Journal of Cellular Immunology

Editorial Open Access

Deubiquitinase as Potential Targets for Cancer Immunotherapy

Xiaoping Xie

During the last few decades, immunotherapy is considered to be an important approach to help our immune system to fight various kinds of diseases, such as tumor. Sometimes, it works very well for some types of cancers, for example: bladder cancer, colorectal cancer, breast cancer and lymphoma.

Review Article Open Access

What Can Go Wrong When Applying Immune Modulation Therapies to Target Persistent Bacterial Infections

Sofiya Micheva-Viteva, Elizabeth Hong-Geller

Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity.

Commentary Open Access

Sticky Interactions in Lupus Nephritis

Radha Nune, Rajalakshmy Ayilam Ramachandran, Jessica Castillo, Chandra Mohan

Cell adhesion molecules (CAM) mediate cell to cell interactions in various body systems including the immune system. The four major families of CAMs include immunoglobulin (Ig) superfamily, cadherins, integrins, and selectins. Most interestingly, several CAMs have emerged in recent years as leading biomarkers of lupus nephritis (LN) based on comprehensive proteomic screens of urine. Proteins belonging to all four families of CAMs have been reported to be upregulated in LN urine.

Commentary Open Access

Intracellular Hyaluronan Synthesis Impairs Hematopoiesis in Diabetes that can be Prevented by Heparin

Andrew Jun Wang, Vincent Charles Hascall

Hyperglycemia in diabetes induces impairment of hematopoiesis, an important consequence in bone marrow (BM) that contributes to chronic complications in advanced diabetes. The alterations to blood cells associated with diabetes mellitus (DM) pathologies have been carefully and extensively documented, but the underlying mechanism(s) is still unclear. Our recent publication indicates that aberrant intracellular synthesis of hyaluronan (HA) by hyperglycemic dividing BM progenitors is the central mechanism involved.

Review Article Open Access

Guardians of Intestinal Homeostasis: Focus on Intestinal Epithelial Cells

Maha M. Elbrashy, Hozaifa Metwally, Tadamitsu Kishimoto

The intestinal epithelium not only facilitates the absorption of nutrients, but also plays a pivotal role in guarding intestinal homeostasis and preventing opportunistic gut microbiome invasions. The intestinal epithelial cells have diverse and coordinated regulatory networks that provide intricate lines of defense, in order to maintain the integrity of the intestinal barrier.

Review Article Open Access

A Review of the Possibility of Nafamostat Mesylate in COVID-19 Treatment

Ji-Young Rhee

Nafamostat mesylate is a synthetic serine protease inhibitor, which inhibits various enzyme systems such as coagulation and fibrinolytic systems, the kallikrein–kinin system, the complement system, and the activation of protease-activated receptors. It also inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)-6 and IL-8 levels in cultured human trophoblasts.

Mini Review Open Access

A Novel Guardian of Telomeres: RIOK2 Regulates Telomerase Activity Through TRiC and Dyskerin Complexes

Merve Akyol, Shrestha Ghosh

Telomeres are repetitive DNA sequences located at chromosomal ends that are crucial for maintaining genomic stability. Telomere lengths are tightly regulated under physiological conditions, disruption of which results in telomere shortening that ultimately leads to telomere biology disorders, such as Dyskeratosis congenita (DC), bone marrow failure syndromes, and Idiopathic Pulmonary Fibrosis (IPF), amongst others. Progressive telomere shortening is also a well-recognized feature of aging.

Review Open Access

The Endothelium: Global Integrator of Vascular-Immune Interactions

Daniel Bergey

Endothelial cells (ECs) are mesodermally-derived modified simple squamous epithelial cells that collectively form the vascular endothelium–the vast living shield that lines the luminal surface of all blood vessels, the lymphatic circuit, and heart. Endothelial cell phenotypes vary among different organs and tissues with regard to specific barrier characteristics, and can be altered by environmental stimuli

Review Article Open Access

Is Platelet Desialylation a Novel Biomarker and Therapeutic Target in Immune Thrombocytopenia?

June Li, Jade A. Sullivan, Heyu Ni

Immune thrombocytopenia is an autoimmune disease predominantly caused by autoantibody mediated platelet and megakaryocyte destruction and or dysfunction, which leads to low platelet counts and risk of bleeding. Currently prognostic biomarkers are underdeveloped and there lacks a gold-standard for therapeutics, which leaves an inexplicable refractory subset of patients which are clinically challenging.

Review Article Open Access

Towards a Better Understanding of Staphylococcus aureus Skin Infections-The Interactions with Dendritic Cells

Aizat Iman Abdul Hamid, Elisabeth Billard, Pascale Gueirard

Staphylococcus aureus (S. aureus) is the leading cause of skin and soft tissue infections in humans. Additionally, local infections further lead to dissemination and colonization of secondary infections sites including the lungs, heart valves and even medical prostheses. It is well known that this bacterial species is capable of altering host immune responses and that long-term protection against S. aureus is not completely effective.

Commentary Open Access

Role of Granulocyte-Colony Stimulating Factor (G-CSF) in Immune Regulation and Neuroprotection

John Dumbuya, Howard Prentice, Jang-Yen Wu

Granulocyte-colony stimulating factor (G-CSF) has been in clinical use for over two decades to enhance hematopoiesis and granulopoiesis to increase the numbers of hematopoietic stem/progenitor cells in patients with neutropenia and patients involved in bone marrow transplantation. G-CSF protein or G-CSF gene therapy has also been shown to have both neuroprotective and neurogenesis function and is quite effective in improving neurological functions in Parkinson’s disease [1], stroke [2-4] and Alzheimer’s disease [5].

Review Article Open Access

Hair Follicle Stem Cells: the Signaling Hub of the Skin

Yongci Tan, Haocai Chang

Hair follicle stem cells (HFSCs) are recognized as multipotential stem cells with exceptional proliferative capacity. Their regulatory effect on skin homeostasis is orchestrated through intricate signaling pathways, including Wnt/β-catenin, transforming growth factor-β/bone morphogenetic protein (TGFβ/BMP), Notch, and Hedgehog.

Mini Review Open Access

Gene Knock-in Strategy for Engineered T-cell Therapy

Qianqian Gao, Renpeng Ding, Cheng-Chi Chao

Genetically engineered T-cell therapy holds great potential for the curative treatment across a series of cancers. However, drug-related safety concerns need to be addressed in the emerging medicine of the future. T cells are engineered through conventional methods like lentivirus, retrovirus or transposon, which randomly integrate exogenous gene cassette into T cell genome, accompanied by the risks of transcriptional silencing, oncogenesis, and variegated transgene expression.

Mini Review Open Access

GRP78: A Multifaceted Role in Cancer Progression and Infectious Disease Transmission

Akane Sato, Etsuro Ito

The 78-kDa glucose-regulated protein GRP78, also known as HSPA5 or BiP, is a heat shock protein 70 family member that promotes functions of the endoplasmic reticulum, such as protein folding and assembly, prevention of aggregation of misfolded proteins, translocation of secreted proteins, and initiation of the unfolded protein response. GRP78 may also be a cancer marker. When small extracellular vesicles containing GRP78 are released from cancer cells, recipient cells exhibit enhanced malignant progression and angiogenesis.

Commentary Open Access

Importance of Ultrasensitive ELISA in Cancer Research

Daiki Makioka, Kanako Iha, Etsuro Ito

The ultrasensitive ELISA method developed by Watanabe and Ito combines sandwich ELISA and thio-NAD cycling to enable the quantitation of trace amounts of proteins. The ultra-traceability provided by this method makes it possible to quantify extremely small amounts of proteins in small extracellular vesicles called exosomes as well as in urine.

Original Research Open Access

Progression of Autoantibodies Anti-Gad and Anti-IA2 in Type 1A Diabetics Aged 5 to 21 Years in Cote d’Ivoire

Aïssé Florence Judith Trébissou, Pascal Sibailly, Amos Ankotché, Mamadou Sanogo, Dinard Kouassi, Marie Thérèse Kouassi, Hatem Masmoudi, Adou Francis Yapo

Type 1A diabetes is an autoimmune disease, the final consequence of a slow and gradual process of ß-cell destruction of pancreatic islet Langerhans cells leading to ketoacidosis in the absence of treatment. This destruction of the β cells, responsible for the production of insulin, begins with the initiation of the autoimmune reaction triggered by certain environmental factors and, after several years of evolution, leads to the clinical signs of the disease when the mass of ß cells

Short Communication Open Access

Role of BCG in Reduction of the Spread and Severity of COVID-19

Amit Raj Sharma, Ankita Semwal, Gitika Batra, Mukesh Kumar, Manisha Prajapat, Ashutosh Singh, Rahul Soloman Singh, Bikash Medhi

The COVID-19 has started from China and spread to all countries within a very short period. The severity of the disease varies from one patient to another as well as one country to another. It depends on the immune status of individuals simultaneously on the quality of the environment and customs of a particular country.

Commentary Open Access

Commentary on “Epigenetically Altered T Cells Contribute to Lupus Flares”

Bruce Richardson

The recently published manuscript entitled “Epigenetically Altered T Cells Contribute to Lupus Flares” summarizes recent advances in our understanding of how the environment alters the immune system to cause flares of systemic lupus erythematosus (SLE) in genetically predisposed people, and why it affects women approximately 9 times more often than men

Review Article Open Access

From Lipase Elevation to Diabetes – Pancreatic Involvement during Immune Checkpoint Inhibition

Sonja C. S. Simon, Jochen S. Utikal

Nowadays, as a standard of care treatment of several cancers, immune checkpoint inhibitors have changed the field of oncology. However, their empowerment of T cell-mediated anti-tumor immunity bears the risk for injury of various organs as a side effect.

Original Research Open Access

Urinary Borrelia Peptides Correlate with the General Symptom Questionnaire (GSQ-30) Scores in Symptomatic Patients with Suspicion of Tick-borne Illness

Sindhu Datla, Sumaiya Irfan, Nicole Trumbull, Rocio Cornero, Ahana Byne, Ghaliah Alluhaibi, Claudius Mueller, Ruben Magni, Weidong Zhou, Barbara Birkaya, Lance Liotta, Alessandra Luchini, Hope McIntyre

Lyme disease, or Lyme Borreliosis, is the most prevalent tick-borne illness in the Northern Hemisphere. It is caused by bacteria in the Borrelia burgdorferi sensu lato (s.l.) complex, which are transmitted to humans through the bite of infected hard bodied ticks, or Ixodes ticks. Post-treatment Lyme disease syndrome (PTLDS) is a significant complication of Lyme disease, characterized by persistent or recurrent symptoms, such as fatigue, musculoskeletal pain, and cognitive issues, which can lead to functional decline. 

Commentary Open Access

A Novel Class of RIP1 or RIP3 Dual Inhibitors

Ting Zhou, Bo Liu

Necroptosis is a form of programed necrosis mediated by receptor-interacting serine/threonine-protein kinase 1 (RIP1) and RIP3 and the subsequent phosphorylation of mixed lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in multiple human diseases such as myocardial infarction, atherosclerosis, and abdominal aortic aneurysms (AAAs). Levels of RIP3 are elevated in the human tissues affected by these diseases.

Commentary Open Access

Glucose Metabolism is a Better Marker for Predicting Clinical Alzheimer’s Disease than Amyloid or Tau

Tyler C. Hammond, Ai-Ling Lin

Alzheimer’s disease (AD) research has long been dominated with communications regarding the amyloid hypothesis and targeting amyloid clearance through pharmacological therapies from the brain. Unfortunately, this research strategy has yielded only one new FDA-accelerated approved therapeutic for early AD, and its clinical benefit still needs to be verified. It may be time to employ a new strategy in AD therapeutics research. Hammond et al. reported that diminished uptake of glucose in the brain is a better marker for classifying AD than beta-amyloid (Aβ) or phosphorylated tau deposition.

Research Article Open Access

Design of a Peptide Against the Interaction Between Immune Response Protein TRAF5 and the Oncoprotein E6 from HPV

Santos GT, Oliveira LN, Moraes D, Araujo DS, Assuncao LP, de Curcio JS, Silva MG, Silva CTX, Barbosa AM, Silva KSF

According to the World Health Organization (WHO), the human papillomavirus (HPV) affects more than 600 million people worldwide, being the most common sexually transmitted disease (STD). There were over 250,000 deaths due to cervical cancer worldwide and most of them took place in developing countries (WHO). There are more than 80 HPV types and more than 40 infect the genital tract

Review Article Open Access

Personalized Neoantigen DNA Cancer Vaccines: Current Status and Future Perspectives

Nadia Viborg, Daniela Kleine-Kohlbrecher, Birgitte Rønø

Tumor mutation-derived neoantigens are considered promising targets for cancer immunotherapy. Personalized vaccines have emerged as an approach to deliver neoantigens and thereby trigger the induction of specific T-cell responses that can find and eliminate tumor cells based on the cell-surface presence of neoantigens. To this end, several neoantigen vaccine formats have provided encouraging results in clinical trials, resulting in neoantigen immunogenicity and clinical benefit.

Commentary Open Access

Recent Advances Show That Abnormal T-Regulatory Cell Function Perpetuates Chronic Inflammatory Arthritis

Charles J. Malemud

The principal mechanism governing immune central tolerance is regulated by T-cells that reside in a pathway wherein the death of immature T-cells is coupled to the development of CD4+ regulatory T (Treg) cells. In that regard, Treg cells undergo development in the thymus or peripheral tissues upon recognition of self-antigens.

Commentary Open Access

Towards a Chemo-immunotherapy to Improve Breast Cancer Immunotherapy

Xia Li, Lixin Ma, Yunhong Hu

Chemo-immunotherapy has shown great promise as a next-generation treatment strategy for established solid tumors. Cheng et al. first developed the PD-L1- and CD44-responsive multifunctional nanoparticles (MNPs) utilizing a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody).

Research Article Open Access

Comparison of Gene Editing versus a Neutrophil Elastase Inhibitor as Potential Therapies for ELANE Neutropenia

Vahagn Makaryan, Merideth Kelley, Breanna Fletcher, Isabella Archibald, Tanoya Poulsen, David Dale

Heterozygous mutations in ELANE, the gene for neutrophil elastase, cause cyclic and congenital neutropenia through the programed cell death of neutrophil progenitors in the bone marrow. Granulocyte colony-stimulating factor is an effective therapy for these diseases, but alternative therapies are needed, especially for patients who do not respond well or are at high risk of developing myeloid malignancies. We developed an HL60 cell model for ELANE neutropenia and previously demonstrated that transient and regulated expression of mutant ELANE causes cell death by accelerated apoptosis.

Commentary Open Access

COVID-19, the Immune System, and Neurological Damage

Sayed Ausim Azizi

The Germ Theory of Disease was solidified in the 19^th century by Louise Pasteur and Robert Koch. They systematically visualized, isolated, and quantified microscopic pathogens as causative agents of diseases and epidemics. Viruses are submicroscopic; therefore, they were discovered later as pathogens by indirect methods.

Review Article Open Access

IL-1 in Abdominal Aortic Aneurysms

Jessica Millar, Elias Nasser, Gorav Ailawadi, Morgan Salmon

Abdominal Aortic Aneurysms (AAA) remain a clinically devastating disease with no effective medical treatment therapy. AAAs are characterized by immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Interleukin-1 (IL-1) has been shown to play role in AAA associated inflammation through immune cell recruitment and activation,

Commentary Open Access

Tenofovir at the Crossroad of the Therapy and Prophylaxis of HIV and HBV Infections

Erik De Clercq

Tenofovir, alias (R)-PMPA, was first divulged as an anti- HIV agent in 1993 [1]. That it would in 2012, become the first antiretroviral agent, approved by the US FDA (Food and Drug Administration) to prevent HIV infection, could have been predicted from the findings of Tsai et al.

Commentary Open Access

Proteomic Functional Signatures during the Priming of Human Th17 Cells

Mohd Moin Khan, Robert Moulder, Riitta Lahesmaa

A combination of regulated responses toward pathogens and minimized autoimmune reactions is needed for the balanced function of the immune system. Amongst the immunologically important CD4+ lymphocytes, T helper 17 (Th17) cells help maintain homeostasis and provide protection against pathogens of fungal or bacterial origins

Review Article Open Access

Essentials of CAR-T Therapy and Associated Microbial Challenges in Long Run Immunotherapy

Muhammad Kalim, Rui Jing, Xin Li, Zhiwu Jiang, Ningbo Zheng, Ziyu Wang, Guo Wei, Yong Lu

Chimeric antigen receptor (CAR)-T cell therapy has shown potential in improving outcomes for individuals with hematological malignancies. However, achieving long-term full remission for blood cancer remains challenging due to severe life-threatening toxicities such as limited anti-tumor efficacy, antigen escape, trafficking restrictions, and limited tumor invasion. Furthermore, the interactions between CAR-T cells and their host tumor microenvironments have a significant impact on CAR-T function.

Commentary Open Access

The Interplay between Transcription Factor SALL4 and Histone Modifiers in Hematopoietic Stem and Progenitor Cells

Hiro Tatetsu, Daniel G. Tenen, Li Chai

Currently, there is a growing need for culturing hematopoietic stem/progenitor cells (HSPCs) ex vivo for various clinical applications such as HSPC transplantation and gene therapy. For many patients with hematologic, genetic, and immune diseases, HSPC transplants can be a life-saving treatment. There are over 20,000 patients in the US receiving HSPC transplantation yearly.

Commentary Open Access

The Long-COVID Syndrome: Neoantigens as Driving Force for the Onset of Autoimmune Diseases

Rolf Marschalek

In the fifth year of the pandemic, SARS-CoV-2 variants continue to unveil new insights into particular mechanism of human immunology but also new clues on the interaction of SARS-CoV-2 proteins with host proteins. Nearly all yet known SARS-CoV-2 variants had the ability to cause a post-infection disease termed the Long COVID (LC) syndrome

Commentary Open Access

Commentary: Experimental Mouse Models of Invasive Candidiasis Caused by Candida auris and Other Medically Important Candida Species

Hong Xin

The study “Experimental Mouse Models of Disseminated Candida auris Infection” provides the first insight into the critical role of C5 in the host antimicrobial defense to disseminated candidiasis caused by C. auris. This study also establishes an inbred A/J mouse model of systemic C. auris infection without drug-induced immunosuppression. C. auris has become the first fungal pathogen causing global public health threat due to its multidrug resistance (MDR) and persistence in hospital and nursing home settings.

Review Article Open Access

TNFAIP8: Inflammation, Immunity and Human Diseases

Suryakant Niture, John Moore, Deepak Kumar

Inflammation can be caused by various environmental factors, including microbial infection and toxic chemical exposure. In response to inflammation, immune cells like macrophages, B and T lymphocytes, fibroblasts, endothelial cells, and various stromal cells secrete soluble polypeptide cytokine Tumor Necrosis Factor Alpha (TNF?)

Commentary Open Access

The Role of Quantification of Glucocorticoid-associated Toxicity in Severe Asthma

PJ McDowell, JH Stone, LG Heaney

Until recently, oral glucocorticoid (GC) therapies were the mainstay of treatment for uncontrolled inflammatory disease across many body systems. The last 30 years, however, have witnessed a transformation in the management of many diseases due to the development of targeted biological agents leading to a reduction, albeit not a removal, of the dependence on oral GCs.

Commentary Open Access

CAR-T cell Goes on a Mathematical Model

Luciana Rodrigues Carvalho Barros, Brendon de Jesus Rodrigues, Regina C Almeida

CAR-T cell immunotherapy is a great advance in hematological cancers treatment. New CARs and therapy schemes are being developed and a mathematical model could contribute to a rational design of treatment. Here we comment and show new results with previously published models of CAR-T cell therapy, emphasizing the contribution of initial tumor load, the proliferation of CAR-T cell and inhibition of CAR-T cell activity by the tumor resulting in different scenarios as tumor escape, equilibrium (stable disease) and tumor elimination.

Mini Review Open Access

Is Interstitial Macrophage Mainly Responsible for Lung Injury in SARS-CoV-2 Infection?

José Guillermo Cabanillas López

The course of the COVID-19 pandemic has led to high mortality rates worldwide, which justifies the development of various research studies aimed at elucidating the physiopathological mechanisms involved in the development of lung injury associated with this disease. The angiotensin-converting enzyme 2 (ACE2) receptor

Commentary Open Access

Spatial Architecture of the Tumor Microenvironment in Immune Checkpoint Inhibitor–Induced Hyper Progressive Bladder Cancer

Ryoichi Maenosono, Kazuki Nishimura, Kensuke Hirosuna, Moritoshi Sakamoto, Masahiko Ajiro, Kazumasa Komura, Haruhito Azuma, Akihide Yoshimi

Muscle invasive bladder cancer (MIBC) is associated with high recurrence and life-threating metastasis. Although the standard therapy for MIBC is a radical cystectomy to prevent metastasis, this approach has been associated with distant recurrence in 75 % of cases and local recurrence in 25 % of cases with a median time to recurrence of 12 months, leading to adverse impact on quality of life

Review Article Open Access

SARS-CoV-2 Infection: The Viral Arms Race and Pattern- Recognition Receptors

Qi Liu, Sensen Chi, Shuai Tan

Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2), the causative agent of COVID-19 respiratory disease, was first identified on 7 December 2019, and quickly spread worldwide. The SARS-CoV-2 belongs to Coronaviridea family, enveloped single-stranded RNA viruses. The family is divided into two subfamilies, the Coronavirinae and the Torovirinae, distinguished by the shape of their nucleocapsids . Virions are roughly spherical and are notable for the large spike (S) glycoprotein that mediate viral entry to the host cell. The subfamily Coronavirinae consists of four genera, the alpha-, beta-, gamma-, and delta-coronaviruses. There are seven coronaviruses that can infect people – four of them causing a common cold (229E, NL63, OC43, HKU1), and three are associated with potentially severe respiratory conditions, namely severe syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the emerging type of SARS-CoV-2, which has 79% sequence homology with SARS-CoV.

Review Article Open Access

The Role of NETosis in Systemic Lupus Erythematosus

Ryan Salemme, Lauren N. Peralta, Sri Harika Meka, Nivetha Pushpanathan, Jessy J Alexander

Systemic Lupus Erythematosus (SLE) is a devastating autoimmune disease that affects women to men at a ratio of 9:1 and is predominant in those of African ancestry. In SLE, the presence of autoantigens results in aberrant immune activation leading to systemic inflammation that predominantly affects the brain, kidneys, blood, and skin. Current guidelines recommend treatment with immunosuppressive drugs like prednisone, cyclophosphamide, azathioprine, and even some antimalarial drugs

Commentary Open Access

Exploring the Potential of Probiotics in Boosting the Immune System's Response to Reduce the Severity of Malaria

Bamgbose Timothy, José de la Fuente

Malaria, caused by various strains of malaria parasites such as Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi, is a major threat to human health worldwide. It is estimated that around 3.3 billion people are at risk of developing this disease [1]. Recent research on the human microbiome has revealed a link between resident microbial communities and the risk of blood parasites, offering potential for microbialbased disease treatments such as probiotics [2].

Commentary Open Access

Prospects of JAK Inhibition in the Framework of Bone Loss

Susanne Adam, Georg Schett, Silke Frey

Cytokine receptors may possess an intrinsic capability for the transduction of signals upon engagement by the respective cytokine ligand. However, if they lack an own intracellular signaling entity, they rely on other signaling machineries. One of the key intracellular signaling molecules mediating cytokine effects on immune cells are Janus kinases (JAKs),

Mini Review Open Access

Inflammation and Aging: The Skin Inflammasome in the Context of Longevity Science

Ekta Yadav, MD, MBA, MS

The skin inflammasome is a critical component of the immune system, pivotal not only in responding to acute threats but also in contributing to the chronic inflammation associated with aging. This review provides an in-depth examination of the molecular mechanisms of the skin inflammasome, detailing its role in dermatological conditions like acne, atopic dermatitis, psoriasis, and hyperpigmentation, as well as its impact on systemic aging

Commentary Open Access

A New Window onto the Pacemaker of the Heart, the Sinus Node, Provided by Quantitative Proteomics and Single- Nucleus Transcriptomics

Mark Boyett, Alicia Lundby

Hypothesis-driven research has dominated biomedical science for at least the past century. There are many papers and grant applications that will have been rejected because they are not hypothesis-driven. For example, Haufe reports that the NIH guidelines for RO1 grants states that “A strong grant application is driven by a strong, solid hypothesis with clear research objectives”.

Commentary Open Access

Sharing Weal and Woe: A Commentary on “Gasdermin E Regulates the Stability and Activation of EGFR in Human Non-Small Cell Lung Cancer Cells”

Limei Xu, Xiangguo Liu

Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of Non-Small Cell Lung Cancer Cells (NSCLC). Chemoresistance to tyrosine kinase inhibitors (TKIs), which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. In the present study, we demonstrate a critical role of gasdermin E (GSDME), an important protein for pyroptosis, in the maintenance of EGFR stability and activation.

Review Article Open Access

The Role of Myeloid Populations during Perinatal Liver Injury and Repair

Anas Alkhani, Sarah Mohamedaly, Amar Nijagal

Perinatal liver inflammation can have life-threatening consequences, particularly in infants and young children. An example of a hepatic inflammatory disease during infancy is biliary atresia (BA), an obliterative cholangiopathy that rapidly progresses to hepatic fibrosis and liver failure.

Review Article Open Access

Naltrexone as a Novel Therapeutic for Diabetic Corneal Complications

Patricia J. McLaughlin, Joseph W. Sassani, Ian S. Zagon

Diabetes is a widespread autoimmune disorder that affects nearly 10% of the adult population in the United States. In addition to the primary disease, there are numerous complications associated with inflammation including abnormalities of the heart, visual system, and peripheral nervous system. More than half of the individuals with diabetes will have one or more ocular related complications such as dry eye disease (DED), keratopathy, or retinopathy.

Original Research Open Access

Anti-inflammatory Activity of the Aqueous Extract of the Mixture of Gossypium hirsutum L. (Malvaceae) and Terminalia catappa L. (Combretaceae)

Aïssé Florence Judith Trebissou, Okpo Jean-Noël Okogni, Adou Francis Yapo

Inflammation is a natural defense response of higher organisms to various external aggressors, such as physicochemical factors or microbial infections. The objective of this work is to enhance a medicinal formula derived from a mixture of Gossypium hirsutum L. and Terminalia catappa L. by evaluating and improving its anti-inflammatory activity. The two plant species selected for this study are Gossypium hirsutum L. and Terminalia catappa L. by evaluating and improving its anti-inflammatory activity

Short Communication Open Access

Dual Expression of GARP in Immune and Glioma Cells: Yet Another Mechanism of Cancer Immune Escape

Emily Trzeciak, Niklas Zimmer, Ella Kim, Jonathan Schupp, Bettina Sprang, Petra Leukel, Fatemeh Khafaji, Florian Ringel, Clemens Sommer, Jochen Tuettenberg, Andrea Tuettenberg

Glioblastomas (GB) are amongst the most lethal human tumors exhibiting a highly aggressive behavior manifested by tumor cell infiltration into surrounding tissue. Furthermore, GBs are notorious for their high degree of resistance to cytotoxic treatments [1-3].

Research Article Open Access

Dysregulated CXCL12 Expression in Osteoblasts Promotes B-lymphocytes Preferentially Homing to the Bone Marrow in MRL/lpr Mice

Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, Xiaoming Fei, Wei Shi

Peripheral circulating B-lymphocytes and B-lymphocytes in the bone marrow (BM) show different responses to lymphotoxic or immunosuppressive agents. We explored the existence of a dysregulated distribution of B-lymphocytes between peripheral and BM compartments and the underlying mechanisms. The percentage of CXC chemokine receptor 4⁺ B (CXCR4⁺ B) cells was decreased in the peripheral blood (PB) and increased in the BM of MRL/lpr mice and SLE patients.

Commentary Open Access

Insulin-like Growth Factor 2: Beyond its Role in Hippocampal-dependent Memory

Paulina Troncoso-Escudero, Rene L. Vidal

The insulin-like peptides family is composed of insulin, insulin-like growth factor 1 (IGF1), and insulin-like growth factor (IGF2), together with IGF binding proteins (IGFBP1- IGFBP6). IGF2 is a single-chain secreted protein of 67 amino acids with important functions in fetal growth and development. IGF2 is the less characterized member of this family, and in mice and rats its expression in the brain occurs during embryonic development and adulthood but declines during aging.

Review Article Open Access

Autism – A Potential Autoimmune Disease Neurodegeneration-Induced Autoantibodies against Neural Proteins

Mohamed B. Abou-Donia

We hypothesize that maternal neurodegeneration, resulting from a chemical, infectious or physical brain injury event, can be causative in the development of autism spectrum disorders (ASD). Following a maternal brain injury event before or during gestation, maternal neural proteins escape the breached blood brain barrier (BBB), triggering the formation of IgG autoantibodies.

Commentary Open Access

Identification of Septic Shock Subgroups for Fluid Strategy Formulation: A Multi-Omics Integrated Approach

Xiong Lei, Zhongheng Zhang

Septic shock is characterized by systemic inflammation, vasodilation, and organ hypoperfusion, often necessitating aggressive fluid resuscitation to restore intravascular volume and improve tissue perfusion. However, the administration of intravenous fluids is a double-edged sword. While it can improve hemodynamics, excessive fluid administration can lead to complications such as fluid overload, pulmonary edema, and dilutional coagulopathy.

Editorial Open Access

Targeting "Do Not Eat Me" Signal CD47 in Cancer Immunotherapy

Sachin Kumar Deshmukh

Cells of the innate and adaptive arm of the immune system including macrophages, natural killer (NK) cells, neutrophils, T cells, and B cells, etc. are crucial for the maintenance of the body’s homeostatic balance and prevention of multiple diseases including cancer.

Research Article Open Access

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase

Lucille M. Yanckello, Brian Fanelli, Scott McCulloch, Xin Xing, McKenna Sun, Tyler C. Hammond, Rita Colwell, Zezong Gu, Aaron C. Ericsson, Ya-Hsuan Chang, Adam D. Bachstetter, Ai-Ling Lin

Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap.

Review Article Open Access

Mechanism, Challenges, and Progresses of Chimeric Antigen Receptors T-cell Cancer Therapy

Adem Hussein, Bedaso Mammo

Cancer is a deadly disease and affects everyone at any level of age. Many people lose hope once they are diagnosed with cancer. This is because there is no effective treatment for it. Till the end of the 19th century, researchers across the world were eager to design effective remedies for this decapitating phenomenon and designed so many interventions even though nothing is compensatory for a malignant tumor; in some cases, the side effects overwhelm the benefits.

Original Research Open Access

The Ability of Neonatal Mice to Develop Immunity to Mycobacterium tuberculosis Shows Sex Differences, with Females Displaying Evidence of an Enhanced Immune Response

Mrinal K. Ghosh, Ameae M. Walker

Using four core genotypes (FCG) mice, we have previously shown a larger number of CD4⁺ and CD8⁺ T cells in the spleens of female mice, a sex difference that develops by postnatal day 7 and is retained through adulthood. This difference in splenic T cell number is a consequence of reduced thymic egress and reduced splenic seeding in male mice, caused in part by the male-specific perinatal surge of testosterone, and in part by Sry, which is overexpressed in this model. 

Review Article Open Access

Role of Perforin-2 in Regulating Type I Interferon Signaling

Gregory V Plano, Noula Shembade

Sepsis is a systemic inflammatory response caused by a harmful host immune reaction that is activated in response to microbial infections. Infection-induced type I interferons (IFNs) play critical roles during septic shock. Type I IFNs initiate their biological effects by binding to their transmembrane interferon receptors and initiating the phosphorylation and activation of tyrosine kinases TYK2 and JAK1, which promote phosphorylation and activation of STAT molecules.

Review Article Open Access

Multiple Roles of the Interleukin IL-17 Members in Breast Cancer and Beyond

Stephane Potteaux, Jacqueline Lehmann-Che, Armand Bensussan, Richard Le Naour, Yacine Merrouche

Interleukin-17 (IL-17) family proteins are involved in the control of infections. When unrestrained, these cytokines contribute to the development of chronic inflammatory diseases. The IL-17 family contains 6 members: IL-17A to F. In this review, we outline the current knowledge on the roles of each IL-17 member on breast cancer.

Mini Review Open Access

The Regulation Impact of Naringenin-loaded Chitosan Nanoparticles on Succinate Dehydrogenase Activity in Cancer Cells

Eman M. Ragab, Abeer A. Khamis, Doaa M. El Gamal, Tarek M. Mohamed

Oxidative phosphorylation dysregulation (OXPHOS) has been demonstrated to be essential for the development of cancer. Therefore, it may be argued that chaperone and deacetylase activities modulate OXPHOS activity. For instance, a complicated network of interactions connects a cell’s bioenergetic features and neoplastic potential through the imbalance of sirtuin 3 (SIRT3) and succinate dehydrogenase (SDH) enzymatic activity in mitochondria.

Review Article Open Access

Teledermatology Before, During, and After COVID-19: A Vital Tool to Improve Access and Equity in Specialty Care

Bina Kassamali, Alice J. Tan, Ellen B. Franciosi, Mehdi Rashighi, Avery LaChance

Since the onset of the COVID-19 pandemic, telemedicine has rapidly expanded across the nation as medical systems have had to shift to providing care through virtual modalities to ensure the safety of patients and staff. Teledermatology, in particular, is wellsuited for telemedicine, with literature supporting its efficacy, equitable quality and accuracy, and cost-effectiveness in comparison to in-person visits.

Review Open Access

Sepsis: A Molecular Odyssey from Infection to Organ Failure

Tamer A. Addissouky

Background: Sepsis arises when an uncontrolled systemic immune response to infection leads to life-threatening organ dysfunction. Despite available therapies, sepsis remains a major global health challenge with high mortality. Further research into molecular mechanisms, diagnostic and prognostic biomarkers, and novel treatments is critical to improve outcomes. 

Research Article Open Access

The Natural History of Post-Chikungunya Viral Arthritis Disease Activity and T-cell Immunology: A Cohort Study

Aileen Yu-hen Chang, Alfonso Sucerquia Hernández, Jose Forero-Mejía, Sarah Renee Tritsch, Evelyn Mendoza-Torres, Liliana Encinales, Andres Cadena Bonfanti, Abigale Marie Proctor, Gary Leonard Simon, Samuel Joseph Simmens, Gary Steven Firestein

Background: Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes arthralgias and arthritis that may last for years. The objective of this study was to describe the arthritis progression and T cell immunology over a two-year period. Methods: A cohort of 40 cases of serologically confirmed CHIKV from Magdalena and Atlántico, Colombia were followed in 2019 and again in 2021. Arthritis disease severity, disability, pain, stiffness, physical function, mobility, fatigue, anxiety, sleep disturbances and depression were assessed. 

Commentary Open Access

Targeting Mesothelin in Pancreatic Ductal Adeno- Carcinoma PDAC

Christopher Montemagno, Gilles Pagès

Pancreatic Ductal Adenocarcinoma (PDAC) represents 90% of all pancreatic malignancies. To date, PDAC is the fourth leading cause of cancer-related death and its incidence is rising to become the second one in the next decade. Two major public health problems, obesity and type 2 diabetes, are important etiology factors involved in PDAC development.

Commentary Open Access

Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III

Saurabh Mishra, Richard J. Maraia

All cellular RNAs are synthesized by evolutionary related DNAdependent multisubunit RNA polymerases (Pols). Bacteria and archaea each use a single Pol to synthesize all their RNAs whereas a hallmark of eukaryotes is three homologous Pols, I, II and III and the associated Pol-specific transcription factors (TFs) to regulate synthesis of different class RNAs. The Pol III system produces high molar amounts of tRNAs and other small ncRNAs by the efficient reuse of its stable transcription complexes after formation on the promoters of its target genes, and the recycling of Pol III itself.

Review Article Open Access

Immunologic Implications for Stroke Recovery: Unveiling the Role of the Immune System in Pathogenesis, Neurorepair, and Rehabilitation

Grace Hey, Siya Bhutani, Maxwell G. Woolridge, Aashay Patel, Anna Walls, Brandon Lucke-Wold

Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke.

Short Communication Open Access

Targeting the PI3K/AKT/mTOR/NFkB Axis in Ovarian Cancer

Alia Ghoneum, Ammar Yasser Abdulfattah, Neveen Said

Ovarian cancer stands as the most lethal gynecologic malignancy and remains the fifth most common gynecologic cancer. Poor prognosis and low five-year survival rate are attributed to nonspecific symptoms at early phases along with a lack of effective treatment at advanced stages. It is thus paramount, that ovarian carcinoma be viewed through several lenses in order to gain a thorough comprehension of its molecular pathogenesis, epidemiology, histological subtypes, hereditary factors, diagnostic approaches, and methods of treatment.

Review Article Open Access

Review of the COVID-19 Risk in Multiple Sclerosis

Farhan Chaudhry, Cristina Jageka, Phillip D. Levy, Mirela Cerghet, Robert P Lisak

The ongoing pandemic of the novel coronavirus of 2019 (COVID-19) has resulted in over 1 million deaths, primarily affecting older patients with chronic ailments. Multiple sclerosis (MS) patients have been deemed particularly vulnerable given their high rates of disability and increased susceptibility to infections. There have also been concerns regarding disease-modifying therapy (DMT) during the pandemic as many DMTs may increase the risk of infection due to some of their immunosuppressive properties.

Commentary Open Access

LncZFAS1 Inhibit MPP⁺-Induced Neuroinflammation Through TXNIP/MIB1 E3 Ubiquitin Ligase/NLRP3 Axis

Peiling Huang MM, Weijun Gong MD

Neuroinflammation is associated with the occurrence and progression of Parkinson’s disease (PD). Nucleotide-binding domain-like receptor protein-3 (NLRP3) is closely related to pyroptosis in PD-related cells and animal models, such as microglia and SH-SY5Y cells. The novel lncRNA ZFAS1 (LncZFAS1) regulates a variety of signaling pathways and participates in the inflammatory response in various diseases.

Short Communication Open Access

MicroRNA Signature Targeting Transient Receptor Potential Channels in the Prognosis and Therapy of Cancer

Giorgio Santoni, Consuelo Amantini, Massimo Nabissi, Federica Maggi, Maria Beatrice Morelli

MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein-coding mRNAs. Numerous miRNAs are expressed in human and 50% of human miRNAs are associated with carcinogenesis. Specific miRNAs are expressed in different cancer tissues and modulation of their expression is associated to different tumor stages and clinical outcomes.

Original Research Open Access

Inflammatory, Functional, and Compositional Changes of the Uterine Immune Microenvironment in a Lymphangioleiomyomatosis Mouse Model

Danielle S. Stiene, Andrew R. Osterburg, Lori B. Corsarie, Nick R. Balzarini, Mario Medvedovic, Michael T. Borchers

Lymphangioleiomyomatosis (LAM) is a rare, female-dominated pulmonary cystic disease. Cysts that develop in LAM are characterized by the presence of smooth muscle-like (LAMCore) cells in the periphery. These cells harbor mutations in Tuberous Sclerosis Complex 1 or 2 (TSC1/2), driving uncontrolled proliferation through the mTORC1 pathway. LAMCore cells originate from an extrapulmonary source. Published data supports the uterine origin of LAMCore cells that metastasize from the uterus to precipitate pulmonary function destruction. Immune evasion is hypothesized to occur to allow seeding of the lungs from the uterus. This evasion specifically involves dysfunctional NK cells to allow aberrant proliferation and migration from the tissue.

Commentary Open Access

A Natural Metabolite and Inhibitor of the NLRP3 Inflammasome: 4-hydroxynonenal

Jinmin Zhang, Bradford C. Berk, Chia George Hsu

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, crucial in the innate immune response, is linked to various human diseases. However, the effect of endogenous metabolites, like 4-hydroxynonenal (HNE), on NLRP3 inflammasome activity remains underexplored. Recent research highlights HNE's inhibitory role in NLRP3 inflammasome activation, shedding light on its potential as an endogenous regulator of inflammatory responses.

Commentary Open Access

Syncytiotrophoblast Extracellular Microvesicles in Preeclampsia

Chirag Ram, Robert W. Hu, Laxminarayana Korutla, Andreas Habertheuer, Prashanth Vallabhajosyula

Preeclampsia, a placental disease, is typically characterized by hypertension and proteinuria in pregnant mothers. There is a need for improved noninvasive detection and diagnosis of this condition. Extracellular microvesicles (EVs), including exosomes, are tissue specific nanoparticles released by many tissue types including the placenta into peripheral circulation.

Research Article Open Access

BIOMODULINA T® Modulates Lymphocyte Compartments in Institutionalized Cuban Geriatric Patients

Imilla Casado Hernandez, Vianed Marsán Suárez, Elizabeth Hernandez Ramos, Yenisey Triana Marrero, Gabriela Diaz Dominguez, Yaneisy Duarte Pérez, Mary Carmen Reyes Zamora, Sahily Estradé Fernandez, Consuelo Amantini, Luis Felipe Heredia Guerra

BIOMODULINA T^® is a biological immunomodulator of natural origin, not blood derived, which promises to be a strategy for immune restoration in the elderly, in the midst of the worldwide epidemiological crisis due to the SARS-CoV-2 virus. This research aimed to determine the changes induced by BT in the distribution of lymphocyte compartments of institutionalized Cuban geriatric patients.

Commentary Open Access

Trade-off and Cardiotonic Steroid Signaling: Natriuresis Maintains Sodium Balance at The Expense of Cardiac Fibrosis

Steven T. Haller, Joseph I. Shapiro

The pivotal work by Zijian Xie provided groundbreaking insights describing that the Na/K-ATPase (NKA), in addition to being an essential ion pump, also functions as a signal transducer with the capability to interact with multiple signaling partners. As an extension of this, our work along with a large body of work from the laboratories of Blaustein and Hamlyn as well as Bagrov and Fedorova, demonstrated that there were two major classes of endogenous NKA ligands or cardiotonic steroids (CTS), those from the cardenolide class such as ouabain and those which were bufadienolide such as marinobufagenin.

Review Article Open Access

Breast Implant-associated Anaplastic Large Cell Lymphoma: A Review with Emphasis on the Role of Brentuximab Vedotin

Anthony Stack, Nadia Ali, Nadia Khan

Breast implant-associated anaplastic large cell lymphoma is a recently recognized complication of textured breast implants. It typically presents as unilateral peri-implant swelling approximately 7-10 years after implantation. While the course is usually indolent, breast implant-associated anaplastic large cell lymphoma may form a locally invasive mass and metastasize to regional lymph nodes or beyond to distant sites.

Commentary Open Access

Non-reducing End of Heparin Tri-saccharide is a Scavenger Tool to Detoxify the Glucose Toxicity in Diabetes

Andrew Jun Wang, Aimin Wang, Vincent Charles Hascall

Heparin is a highly sulfated, hence highly polyanionic, glycosaminoglycan with a repeating disaccharide that contains a hexuronic acid, and it has been used as an anticoagulant clinically for more than half a century. Daily IP injections of small amounts of heparin in the STZ diabetic rat prevented these pathological responses even though the animals sustained hyperglycemic levels of glucose throughout.

Commentary Open Access

Can Molecular Biomarkers be Utilized to Determine Appropriate Adjuvant Therapy in Early-Stage Non-Small Cell Lung Cancer (NSCLC)?

Prashanth Ashok Kumar, Alina Basnet, Stephen Graziano

Early-stage NSCLC, encompassing resectable stage I-III  are curable, and represents 25% of all lung cancers. The management of non-metastatic NSCLC is a rapidly changing area of clinical oncology, where utilization of molecular biomarkers has become a cornerstone in informing appropriate management. In current clinical practice, adjuvant chemotherapy is recommended after surgical resection for tumors ≥ 4 cms in size (AJCC 7th stage IB, AJCC 8th stage IIA, and higher stage groups thereafter).

Commentary Open Access

Immunomodulatory Effects of Cell Therapy after Myocardial Infarction

Joseph B Moore 4th, Marcin Wysoczynski

Myocardial infarction (MI) due to coronary artery stenosis compromises vascular endothelial integrity and increases vascular permeability. Concurrently, ensuing myocardial tissue death and necrosis results in the release of danger associated molecular patterns (DAMPs), cytokines, chemokines, bioactive lipids, as well as activation of the complement cascade. 

Commentary Open Access

Fluoxetine is Antimicrobial and Modulates the Antibiotic Resistance Status of Bacteria

Alison M Mackay

The ability of mobile genetic elements to transfer drug resistance between bacteria can cause the rapid establishment of multi-drug resistance (MDR) [1,2], and human infection caused by multi-resistant, rather than susceptible organisms increases the likelihood of death [3]. 

Review Article Open Access

T cell-Intrinsic Peripheral Tolerance: A Checkpoint Target to Treat Autoimmunity

Nasser Gholijani, Gholamreza Daryabor, Fatemeh Rezaei Kahmini

Recent advances highlight the importance of intrinsic peripheral tolerance in the maintenance of a steady state. Peripheral tolerance is tightly regulated and any alteration in its biological process contributes to the breakdown of immune tolerance and induction of autoimmunity. Recent evidence related to T cell tolerance mechanisms inspired researchers to treat autoimmunity via modulation of tolerant checkpoints that are involved in intrinsic T-cell tolerance such as ignorance, anergy, exhaustion, and senescence. 

Short Communication Open Access

IL-10 Responsiveness and Anti-TNF Therapy in Inflammatory Bowel Disease

Felicia M. Bloemendaal, Charlotte P. Peters, Anje A. te Velde, Cyriel Y. Ponsioen, Gijs R. van den Brink, Manon E. Wildenberg, Pim J. Koelink

Inflammatory bowel disease (IBD) is a multifactorial disease in which both genetic and environmental factors play an important role, although the precise cause remains obscure. It is clear that both the innate and adaptive immunity are involved in acquiring mucosal immune homeostasis in the intestine, which is dysregulated in IBD.

Commentary Open Access

A Nonagenarian’s View of Dietary Impacts on Cellular Immunology

Bill Lands

Fatty acids and their esters bind to proteins and lipids rather than being solvated molecules like most metabolites. Some selective lipid-protein interactions can override expected lipidlipid interactions of cell membrane “fluidity” in determining cell physiology. 

Mini Review Open Access

Would It be Possible for a SARS-CoV-2 Infection to Affect the Male Reproductive System?

Kaveh Rahimi, Akram Ebrahimifar, Mehri Rahimi

The male reproductive system may be affected by the systemic infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The precise mechanisms of male reproductive impairment are not well known. There are two possible mechanisms for the effect of SARS-CoV-2 on the male reproductive system either directly through the impact of the angiotensin-converting enzyme 2 (ACE2) receptor 

Commentary Open Access

A novel therapeutic strategy for antifibrotic based on a new gene NS₅ATP₉

Jing Zhao, Jun Cheng

In this article, we introduced a screening of anti-fibrotic drugs focused on new genes. More precisely, we screened and cloned 127 new genes, reporting on a potential target gene and two promising drugs for fibrosis. Among 127 genes, hepatitis C virus nonstructural protein 5A transactivated protein 9 (NS5ATP9), which expression is significantly upregulated by tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide fumarate (TAF), suppresses hepatic stellate cells (HSCs) and HFL1 cells (lung fibroblasts) activation.

Commentary Open Access

M1 Macrophages are More Susceptible to Necroptosis

Qin Hao, Steven Idell, Hua Tang

Macrophages play a crucial role in host innate immune defense against infection and tissue injury. Although macrophage activation and polarization has been well studied, we know less regarding the role of macrophage activation/polarization in inflammationassociated necrotic cell death. By using bone marrow-derived macrophages, we have recently demonstrated that M1 macrophages are much more susceptible than M0 and M2 subtypes of macrophages to necrotic cell death.

Commentary Open Access

Designing Anti-Viral Vaccines that Harness Intrastructural Help from Prior BCG Vaccination

Tony W. Ng, Steven A. Porcelli

Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths.

Review Article Open Access

Advances of Immune Cells in the Pathogenesis and Targeted Therapy of Systemic Lupus Erythematosus

Junyue Fang, Li Lin, Xiaoyun Xiao, Jingwei Tian, Meng Zhang, Phei Er Saw

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease reflecting an imbalance between regulatory and effector immune responses. With the rapid development of molecular biology and multi-omics, the pathogenesis of SLE has been gradually elucidated. In particular, imbalances and abnormalities in immune cell function have been shown to play an important role in the development of SLE. Understanding the specific pathogenesis of SLE is the basis for targeted therapy against specific targets. 

Original Research Open Access

Modeling TCIRG1 Neutropenia by Utilizing Patient Derived Induced Pluripotent Stem Cells

Vahagn Makaryan, Merideth Kelley, Audrey Anna Bolyard, Chris Cavanaugh, Jennifer Hesson, Julie Mathieu, Michael J. Lenaeus, David C. Dale

Congenital neutropenia is characterized by a reduced neutrophil count, decreased innate immunity and increased susceptibility to recurrent infections. While congenital neutropenia has various genetic causes, recent studies have linked TCIRG1 mutations to this condition. TCIRG1, a key component of the vacuolar ATPase (V-ATPase) complex, is essential for osteoclast function, but its role in hematopoiesis remains unclear. We previously identified heterozygous TCIRG1 mutations, including R736S, R736C, R736P, and E722D, in individuals with congenital neutropenia.

Commentary Open Access

Friend or Foe? Opposing Functions of O-GlcNAc in Regulating Inflammation

Miranda Machacek, Chad Slawson, Patricia J. McLaughlin

Effector CD4⁺ T cells (i.e. Th1, Th2, Th17) are essential in the adaptive immune system’s specific elimination of different classes of pathogens, such as viruses, bacteria, and parasites, while regulatory T cells shut these inflammatory responses off once a pathogen has been cleared. Interestingly, effector T cells preferentially utilize

Commentary Open Access

Structural Consequences of Variation in SARS-CoV-2 B.1.1.7

David A. Ostrov

New globally circulating SARS-CoV-2 strains are causing concern about evolution of virus transmissibility, fitness and immune evasion mechanisms. A variant emerging from the United Kingdom called SARS-CoV-2 VUI 202012/01, or B.1.1.7, is thought to exhibit increased transmissibility that results from replication 4-10 times faster than the original Wuhan virus (Wuhan-Hu-1).

Review Article Open Access

Antimicrobial Prophylaxis in Lymphoma by Chemotherapy Regimen

Kamen W. Kossow, Joseph G. Bennett, Marc S Hoffmann

Treatment of lymphomas involves a wide variety of chemotherapy, immunotherapy, and targeted-agents tailored to disease biology and patient characteristics. Each of these regimens carry their own risk of opportunistic infections in an immunocompromised population. In addition to the treatment associated immunosuppression, lymphoma itself is immunosuppressive. Lymphoma associated immunosuppression is secondary to increased production of abnormal lymphocytes

Commentary Open Access

Commentary on the Clinicopathological Characteristics Prognosis and Immune Microenvironment Mapping in MSI-H/ MMR-D Endometrial Carcinomas

Yu-e Guo, Guofang Chen

TME contains various cell types (malignant cells, immune cells, fibroblasts, endothelial cells, etc.) and extracellular components (cytokines, growth factors, hormones, extracellular matrix, etc.). Tumor heterogeneity, characterized by each tumor’s distinct TME cellular composition and states and the interplay between these components, may play a critical role in tumor initiation, progression, therapeutic efficacy, and patient survival.

Short Communication Open Access

M₁ and M₂ Macrophages Polarization via mTORC₁ Influences Innate Immunity and Outcome of Ehrlichia Infection

Ibrahim Ahmed, Nahed Ismail

Human monocytic ehrlichiosis (HME) is an emerging life-threatening tick-borne disease caused by the obligate intracellular bacterium Ehrlichia chaffeensis. HME is often presented as a nonspecific flu-like illness characterized by presence of fever, headache, malaise, and myalgia. However, in some cases the disease can evolve to a severe form, which is commonly marked by acute liver injury followed by multi-organ failure and toxic shock-like syndrome.

Review Article Open Access

Pregnancy Specific Glycoproteins: A Possible Mediator of Immune Tolerance of Cancers

Junfei Zhao, Raul Rabadan, Arnold J. Levine

Cancer immunotherapy relies upon the immune system recognizing and killing cancer cells. Tumors can elude recognition by readapting existing mechanisms of immune control and suppression. Here we explore the hypothesis that cancers repurpose the immune suppression employed during pregnancy to protect the allogeneic fetus. Those mechanisms are reviewed and shown to be employed both in pregnancy and by tumors.

Commentary Open Access

FLIP-expressing myeloid cells as driver of systemic immune disorders

Alberto Atanasio, Davide Rizzini, Stefano Ugel

The role of FLIP as a moonlighting protein is becoming progressively evident since this protein is often involved in various processes correlated to aberrant immunological responses independently from its function as master anti-apoptotic regulator. It has been uncovered that FLIP drives the acquisition of immunosuppression and inflammation-associated pathways in myeloid cells.

Mini Review Open Access

Neuroimmunopathology in Coenurosis: A Mini Review

Eman Mohamed Emara, Asmaa Hassan Bedair, Omnia Mostafa Elaafy, Alyaa Atef Abd ElRazik, Donia Sobhy Mohammed Bishr, Omar Ashraf Aladawy, Hamdy Ahmed Shahin, Saeed El-Ashram

Coenurosis is a socioeconomically significant zoonotic disease. The neuroimmunopathology of this disease is complex, involving a dynamic interplay between the parasite and immune system dynamics of several hosts. Although current diagnostic and treatment approaches remain inadequate, there is some solace in the recent investigations leading to proper prevention and control mechanisms of coenurosis with the One Health philosophy, integrating veterinary medicine, parasitology, immunology, community medicine, and public health—while also addressing other neglected trematode pathogens.

Commentary Open Access

Targeting Monocyte Abnormalities in Systemic Lupus Erythematosus through Omics-Based Drug Repurposing

Panagiotis Garantziotis, Dimitrios Nikolakis, Eleni Frangou, George Bertsias, Dimitrios T. Boumpas

Systemic Lupus Erythematosus (SLE) is a complex disease marked by extensive immune system dysfunction, culminating in a diverse spectrum of clinical phenotypes of varying severity. Despite the significant advancements in elucidating the pathogenesis of the disease, the management of SLE remains largely empirical with attainment of low disease activity and remission targets being an infrequent outcome among patients.

Commentary Open Access

Commentary on Updated Insight into the Role of Th2-Associated Immunity in Systemic Lupus Erythematosus

Xinyue Hou, Jinjin Chu, Shuhao Liu, Shuyu Jin, Jiamei Sun, Hui Wang, Haibo Li, Wei Liu, Chunxiang Chai, Sue Zhang, Donghua Xu

Systemic lupus erythematosus (SLE) is a common autoimmune disease caused by multiple factors. The pathogenesis of SLE remains unclear. Helper T cell 2 (Th2 cell) is essential for humoral immunity, which participates in regulating type 2 immune response by producing typical cytokines of interleukin (IL)-4, IL-5, and IL-13. It is well known that Th2-associated immunity plays a vital role in autoimmune diseases, including SLE.

Mini Review Open Access

The Role of Innate Immune System: A Crosstalk between Invertebrates and Humans

Camile Dias Avelino, Yorran Hardman Araújo Montenegro

Innate immunity is the oldest form in evolution and is present in all multicellular organisms, including vertebrates and invertebrates. Although humans are the most recent evolutionary phylum, there is abundant evidence of a genetic inheritance shared between invertebrates and humans. There is correspondence between molecular pathways associated with the recognition systems of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) and Peptidoglycan recognition proteins (PGRPs).

Review Article Open Access

CD₁₄₆-Positive Tumors are Associated with Venous Thromboembolism

A. Joshkon, J. Stalin, W. Traboulsi, L. Vivancos-Stalin, M. Nollet, R. Lacroix, R.Bachelier, F. Dignat-George, A. Bertaud, A.S. Leroyer, H. Fayyad-Kazan, N. Bardin, M.Blot-Chabaud

The role of CD146 and its soluble form have been intensely reviewed in the processes of cancer and inflammation. However, how CD146 is linked to coagulation and thrombotic events remains unclear. The aim of this paper is to shed light on this topic and clarify the contribution of CD146 as a procoagulant factor.

Short Communication Open Access

Microbial Resistance to Photodynamic Therapy

Alison M Mackay

Microbial resistance to antibiotics has become a major area of research having caused over a million human deaths in 2019. At present, lower respiratory infection is the most burdensome disease. Antimicrobial Photodynamic Therapy (PDT) is regularly reported not to cause resistance in any pathogen, and to eradicate both microbes that are susceptible to antibiotics and those that are resistant.

Commentary Open Access

Homology-Independent Targeted Insertion (HITI) for Therapeutic T-Cell Engineering

Vimal Keerthi, Hyatt Balke-Want, Ramya Tunuguntla, Steven Feldman

In this commentary we discuss our recent work on delivering an anti-GD2 CAR (chimeric antigen receptor) via homology independent targeted insertion (HITI) using the CRISPR/Cas9 technology. HITI relies on Non-Homologous End Joining (NHEJ) that is predominantly exploited by both dividing and non-dividing cells to repair double stranded DNA breaks (DSBs). We explore considerations when using HITI based strategies. Furthermore, we discuss a method for post-HITI CRISPR EnrichMENT (CEMENT) within the context of large-scale clinical manufacturing of non-viral CAR-T cells.

Commentary Open Access

IL-22-mediates Cross-talk between Tumor Cells and Immune Cells Associated with Favorable Prognosis in Human Colorectal Cancer

Raoul André Droeser, Giandomenica Iezzi

The positive prognostic role of the immune environment in colorectal cancer is widely accepted. However, there are few data about the prognostic significance of interleukin-22 in human colorectal cancer which is still debated.

Commentary Open Access

Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas

Brittany S. Bruggeman, Desmond A. Schatz

Type 1 diabetes has historically been described as an endocrine (β-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, β-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells.

Commentary Open Access

The Aryl Hydrocarbon Receptor as a Possible Novel Immunotherapy Target in Myeloma

Olivia Kerekes, Paloma Gonzalez, Don M Benson Jr, Abdullah Khan

Epidemiologic studies have demonstrated a possible association between exposure to environmental aromatic hydrocarbons and the development of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). These aromatic hydrocarbons bind the aryl hydrocarbon receptor (AHR) expressed by plasma cells that seem to promote development and survival of malignant cells.

Review Article Open Access

Persistence, Pathogenicity and Plasticity: The Role of IL-23 in Th17 Fate

Jens C. Kleiner, Christian F. Krebs

For a long time Th1 cells were considered the key players in the induction of inflammation and progression of disease in autoimmune diseases. With the discovery of IL-17-producing CD4+ T cells (Th17) being abundant at inflammation sites, this soon changed. Investigating this new T helper subset, it became clear that in comparison to Th1 and Th2 cells, Th17 cells have an increased tendency to change their phenotype and therefore become either more pathogenic or immunoregulatory.

Commentary Open Access

From Bench to Body: Protective Candida-specific Monoclonal Antibodies Show In vivo and Translational Potential

Hong Xin

Candida auris is a multidrug-resistant fungal pathogen that presents a growing global health challenge, particularly due to its ability to cause invasive bloodstream and deep-seated infections in vulnerable patients. Monoclonal antibody (mAb)-based immunotherapy offers a novel and targeted approach to overcoming the limitations of current antifungal treatments. This commentary highlights the protective efficacy of Candida-specific mAbs, C3.1, 6H1, and 9F2, in in vivo mouse models of disseminated candidiasis.

Short Communication Open Access

Understanding the Role of the Scabies Mite Microbiota in the Development of Novel Control Strategies

Sara Taylor, Katja Fischer

With a global prevalence of approximately 300 million people, scabies is one of the most common dermatological infectious diseases worldwide, and was recognised as a neglected tropical disease in 2017 by the World Health Organisation. Scabies is especially prevalent in economically disadvantaged communities and disproportionately affects children in poor and overcrowded living conditions.

Research Article Open Access

Basophil Activation Tests BAT: Degranulation, Cytometry and Chemotaxis in Drug Allergy

Maria de Lourdes Irigoyen Coria, María Isabel Rojo Gutierrez, David Solís Hernández, Ruben Humberto Meyer Gómez, Isabel Leyva Carmona, Jaime Mellado Abrego, Gloria Castillo Narváez, Isabel Guerrero Vargas

To Increase the knowledge on Drugs Hypersensitivity Reactions (DHRs); activation, development of reliable diagnostic tests for better: selection of studies, diagnosis, identification of risk groups, prevention, cross-reactions, severs skin drug reactions and alternative therapeutics.

Review Article Open Access

Evolution of the Classification and Management of Smoldering Multiple Myeloma

Dennis D. Lee, Faith E. Davies, Gareth J. Morgan

The evolving molecular landscape of Smoldering Multiple Myeloma (SMM) has underscored its complex nature and the urgent need for more refined diagnostic and treatment strategies. With an increased risk of progression to Multiple Myeloma (MM), it has become important to identify patients at the highest risk of progression for interception strategies. Risk evaluation has been a constantly moving target with rapidly changing approaches to classification being based predominantly based on imaging and biochemical data thus far.

Commentary Open Access

Estrogen Receptor Alpha Contributes to Intestinal Inflammation in a Murine Model of Ileitis

Alyssia V. Broncano, Wendy A. Goodman

Inflammatory bowel diseases (IBD) are inflammatory conditions characterized by chronic and recurrent intestinal inflammation. IBD affects nearly five million people worldwide, with an estimated prevalence of 245.3 cases per 100,000 people in the United States alone. The incidence of IBD is steadily increasing in industrialized countries and is appearing more often developing countries, contributing to its rise as a global disease burden.

Review Article Open Access

Can Vaccines Stop Cancer Before It Starts? Assessing the Promise of Prophylactic Immunization Against High-Risk Preneoplastic Lesions

Tamer A. Addissouky, Ibrahim El Tantawy El Sayed, Majeed M. A. Ali, Yuliang Wang, Ayman El Baz, Ahmed A. Khalil, Naglaa Elarabany

Background: Cancer remains a leading cause of mortality with modest declines, highlighting the need for more efficacious prevention strategies like early immunological intervention against premalignant disease.

Commentary Open Access

The First Viral Expression Model in Human Induced Pluripotent Stem Cells to Observe Enteroviral Infections In vitro

Stefan Peischard, Huyen Tran Ho, Nathalie Strutz-Seebohm, Guiscard Seebohm

Viruses recently caused global outbreaks of potentially severe diseases. The newly recognized corona virus, which is causing SARS-CoV-2 is the most recent example for this scenario. Potentially severe but not as prominent as the corona virus is the Coxsackievirus B3 (CVB3), which can cause fatal outcomes of myocarditis, meningitis, encephalitis and diabetes type 1 due to chronical infections of the heart, the brain, and the pancreas.

Commentary Open Access

CAR Therapy for T-cell Malignancies

Andrew Cinquina, Jia Feng, Hongyu Zhang, Yupo Ma

The introduction of chimeric antigen receptor (CAR) immunotherapy has been revolutionary in the treatment of hematological malignancies.

Commentary Open Access

Efferocytosis and Anthrax: Implications for Bacterial Sepsis?

Joshua S. Mytych, Zijian Pan, A. Darise Farris

Bacillus anthracis (Ba) is a gram-positive, rod-shaped, spore- and toxin-forming bacterium. While mainly an herbivore pathogen, human infection with Ba spores can occur through a number of routes including cutaneous, gastrointestinal, injectional, or inhalational. The deadliest form of anthrax exposure is through inhalation of Ba spores, leading to systemic dissemination of the bacteria, with mortality ranging from 45% to 90%. 

Mini Review Open Access

Association of Smoking and Crohn's Disease: An Update

Alejandro Mínguez, Pilar Nos

The relationship between smoking and inflammatory bowel disease (IBD), which has been widely studied for years, is complex and different in Crohn's disease (CD) and ulcerative colitis (UC). The negative effect on CD, not only on disease progression and post-surgical recurrence, but also on post-surgical complications after intestinal resection, on its influence on the reservoir and on the modification of the natural evolution of CD towards fistulizing and stenosing forms, makes a proper approach to the problem imperative.

Letter to the Editor Open Access

Examining the Relationship between SARS-CoV-2 Infection and Type 1 Diabetes: A Reanalysis of Recent Findings

Yongxin Zhang, Ying Wang

Type 1 diabetes (T1D), an autoimmune disease mediated by T cells, has long been associated with various viral infections [1-4]. Among these infections, enterovirus infection [5-7] was more consistently reported to contribute to the development of T1D

Commentary Open Access

PD-L1 as a Novel Mediator of Lung Fibroblast to Myofibroblast Transition

Xia Guo, Guoqing Qian

Idiopathic pulmonary fibrosis (IPF) is an incurable disease that affects approximately 3 million people worldwide. Although two drugs (nintedanib and pirfenidone) have been approved for treatment of IPF, currently there is a lack of effective pharmacotherapy that could stop the progression or offer a cure for this devasting disease.

Commentary Open Access

CRISPR Taking the Front Seat in Immunotherapy

Saad S. Kenderian, Andrew D. Badley

CRISPR (clustered regularly interspaced short palindromic repeats) technology has dramatically simplified genome editing and is widely applicable in both basic research and therapeutic areas. The basic principle of CRISPR relies on the use of guide RNA which is designed to bind to the DNA sequence of interest along with a CRISPR-associated (Cas) endonuclease which introduces a double-stranded DNA break (DSB) at that site.

Research Article Open Access

Expansion of Proteome-wide Coxiella burnetii Comparative T-cell Epitope Prediction to Include Small Ruminant Hosts

Paige C. Grossman, David A. Schneider, Robert Kirkpatrick, Stephen N. White, Lindsay M.W. Piel

Coxiella burnetii is the causative agent of Q fever, a human disease that can be acquired from livestock. Diseases caused by this organism have caused great losses in livestock and human health. No vaccine is approved for use in the United States, and formalininactivated whole-cell vaccines pose a significant manufacturing risk for biocontainment.

Review Article Open Access

Ca²⁺/calmodulin-dependent Protein Kinases in Leukemia Development

Changhao Cui, Chen Wang, Min Cao, Xunlei Kang

Ca²⁺/ calmodulin (CaM) signaling is important for a wide range of cellular functions. It is not surprised the role of this signaling has been recognized in tumor progressions, such as proliferation, invasion, and migration. However, its role in leukemia has not been well appreciated. The multifunctional Ca²⁺/CaM-dependent protein kinases (CaMKs) are critical intermediates of this signaling and play key roles in cancer development.

Letter to the Editor Open Access

Improvement of the Specificity of the Indirect BAT for the Diagnosis of Peanut Allergy; the BA(Blocking Antibodies)-BAT

Janneke Ruinemans-Koerts, Monique van Uum-Otters, Don van Baar, Joost van Neerven, Judit Wesseling

The direct and indirect Basophil Activation Test (BAT) are well known for their capacity to predict the presence of an IgEmediated peanut allergy resulting in a reduction of expensive and time-consuming oral food challenge (OFC) tests. Although the BAT is a promising test, false-positive and false-negative outcomes are observed .

Review Article Open Access

T lymphocytes in Aging: CD38 as a Novel Contributor between Inflammaging and Immunosenescence

Wendolaine Santiago-Cruz, Fabio García-García

CD38 is a transmembrane protein expressed in immune and non-immune cells involved in nicotinamide adenine dinucleotide (NAD⁺) consumption, cyclic Adenosine Diphosphate Ribose (cADPR) generation, and calcium mobilization by its enzymatic activity. It also promotes an activated and pro-inflammatory phenotype in immune cells. Senescence is a cellular state of cell growth arrest accompanied by senescent-associated secretory phenotype (SASP) products.

Commentary Open Access

Lung-targeted SERCA_2a Gene Therapy: From Discovery to Therapeutic Application in Bleomycin-Induced Pulmonary Fibrosis

Malik Bisserier, Lahouaria Hadri

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by an accumulation of scar tissue within the lungs and the common presence of usual interstitial pneumonia. Unfortunately, only a few FDA-approved therapeutic options are currently available for the treatment of IPF and IPF remains associated with poor prognosis. Therefore, the identification of new pharmacological targets and strategies are critical for the treatment of IPF.

Commentary Open Access

Manufacturing of Human T-lymphoid Progenitors from Two Different Hematopoietic Stem Cell Sources and Perspective for New Immunotherapies

Pierre Gaudeaux, Ranjita Devi Moirangthem, Pauline Rault, Hanem Sadek, Francesco Carbone, Marieke Lavaert, Akshay Joshi, Tom Taghon, Isabelle André, Olivier Nègre, Tayebeh-Shabi Soheili

The adaptive immune system depends on the efficient response of lymphocytes, protecting the organism from infection or malignant diseases. T-cell immunodeficiency, innate or acquired, put the patient at risk for developing opportunistic infections and cancers.