Journal of Cellular Immunology

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. 

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.

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.

Commentary Open Access

Risk of Venous Thrombotic Events in Systemic Lupus Erythematosus Patients: Genetic Insights

Maria I. Zervou, George N. Goulielmos

Various studies have reported a strong association between different autoimmune diseases or infection-mediated disorders and an increased risk for venous thromboembolism (VTE). Particularly, patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) have been found to be associated with VTE. The aforementioned studies posed an intriguing question concerning the putative role of a shared genetic background as regards with the co-occurrence of VTE with RA, AS or PsA. 

Review Article Open Access

Immunotherapy in the Management of Hodgkin Lymphoma: Time for Immunotherapy for All?

Coen J. Lap, Joseph L. Roswarski

Hodgkin lymphoma (HL) is a lymphoid malignancy of germinal center B cell origin. Conventional chemotherapy with or without radiation induces high cure rates but these treatments can have relevant long-term toxic side effects. As a result, there remains a lot of debate about the optimal management of these patients, especially for limited-stage disease. The last two decades have resulted in a greater understanding of the underlying biology of HL, including the presence of an aberrant phenotype on the tumor cells and the necessity of immune escape.

Original Research Open Access

Evaluating the Role of the Renin-angiotensin System in COVID-19: Implications for ACE Inhibitor and ARB Use During SARS-CoV-2 Infection

Sarah Renee Tritsch, Evelyn Mendoza-Torres, Mónica Gómez-Pulido, Jairo Castellar-López, Rebecca Lynch, Carlos Andres Herrera Gomez, Hana Akselrod, Adrienne Poon, Samuel Joseph Simmens, Christopher N. Mores, Gary Leonard Simon, Lauren C. Ray, Sarah Conway, Aileen Yu-hen Chang

This study aimed to investigate the role of the renin-angiotensin system (RAS) in COVID-19, particularly focusing on key components such as ACE, ACE2, and their related peptides, angiotensin-(1-7) and angiotensin-(1-9). Using serum samples from healthy controls and both non-severe and severe COVID-19 patients, ELISA assays revealed no significant differences in these RAS components between the groups.

Original Research Open Access

Medicinal Plant Use in Post-chikungunya Viral Arthritis Disease Patients in Brazil: A Cross-sectional Study

Ramão Luciano Nogueira Hayd, Tiago Matos Dourado, Jose Forero-Mejía, Jose Gabriel Lara-Amador, Aileen Yu-hen Chang

Chikungunya virus (CHIKV) is an alphavirus spread by mosquitoes that is endemic to the Amazon region of Brazil. One significant outbreak of CHIKV occurred between 2014 and 2018 In Roraima, Brazil, with 5,928 reported cases of chikungunya, of which 3,719 were confirmed in Boa Vista after phylogenetic analysis showed that the ECSA strain of the virus caused the outbreak in 2017. In a cross-sectional study of participants affected by this CHIKV outbreak in Roraima, the most common symptoms reported in the initial infection period were fever, joint pain, headache, myalgia, and eye pain. 

Original Research Open Access

Development of a Chikungunya Arthritis Disease Activity Score (CHIK-DAS) Based on a Prospective Cohort Study

Aileen Yu-hen Chang, Samuel Joseph Simmens, Hugh Watson, Richard L. Amdur, André Siqueira, Abigale Marie Proctor, Sarah Renee Tritsch, Carlos Andres Herrera Gomez, Liliana Encinales, Alfonso Sucerquia Hernández, Jose Forero-Mejía, Alejandro Jaller, Juan Jose Jaller, J. Kennedy Amaral, Ilana Heckler, Gary Leonard Simon, Larry Moreland, Andres Cadena Bonfanti, Gary Steven Firestein

Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos, primarily Aedes aegypti and Aedes albopictus, that causes a debilitating febrile illness called chikungunya fever (CHIKF). CHIKF usually presents in two phases, starting as an acute illness, characterized by high fever, polyarthralgia and polyarthritis, headache, maculopapular skin rash, sometimes pruritic, and severe fatigue, commonly accompanied by anorexia, nausea, vomiting and diarrhea. This first phase usually resolves within 5-14 days.

Review Article Open Access

Epidemiology, Symptoms and Pathophysiology of Long Covid Complications

Chongyang Zhang, Chiung-Yu Hung, Chia George Hsu

Long COVID, or post-acute sequelae of SARS-CoV-2 infection, reports to affect a significant proportion of COVID-19 survivors, leading to persistent and multi-organ complications. This review examines the epidemiology, symptoms of long COVID complications, including cardiac, hematological, vascular, pulmonary, neuropsychiatric, renal, gastrointestinal, musculoskeletal, immune dysregulation, and dermatological issues

Commentary Open Access

Innate Immune Sensors Spying Microbial Hideouts! OAS1 - ‘Stalwart Defender’ or ‘Hidden Enemy’?

Suparna Dhar, Sourish Ghosh

OAS1 plays a critical role in host-pathogen interactions by balancing translational shutdown to limit microbial replication while producing antimicrobial components. Host RNA sensors detect microbial nucleic acids, initiating an interferon-mediated innate immune response that induces ISGs to inhibit replication and shape adaptive immunity. OAS1 enhances the translation of selective mRNAs, producing proteins with antimicrobial properties.

Research Article Open Access

Evaluation of Neutrophil Elastase Inhibitors as Potential Therapies for ELANE Associated Neutropenia

Vahagn Makaryan, Merideth Kelley, Audrey Anna Bolyard, Gobind Chugh, David C. Dale

Neutrophil elastase (ELANE) mutations are the most common cause of cyclic (CyN) and congenital neutropenia (SCN), two autosomal dominant disorders causing recurrent infections due to impaired neutrophil production. Granulocyte colony-stimulating factor (G-CSF) corrects neutropenia but has adverse effects, including bone pain and in some cases, an increased risk of myelodysplasia (MDS) and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation is an alternative but is limited by its complications and donor availability. Alternative therapies are needed, particularly for patients with poor responses to G-CSF and those at higher risk of MDS/AML.

Perspective Open Access

Telling Your Research Story

Houmam Araj

It is impossible for a person to begin to learn what he thinks he already knows. That's what Epictetus, the Greek Stoic philosopher, taught us two millennia ago. Yet somehow that lesson never made it to some of us – myself included. Rather, we have to learn it on our own and pay the appropriate price

Review Article Open Access

Polyamines: Key Players in Immunometabolism and Immune Regulation

Shanmuga S. Mahalingam, Pushpa Pandiyan

Polyamines are small organic molecules ubiquitously present in all living organisms and function as crucial regulators of biological processes ranging from fundamental cellular metabolism to immune regulation. Dysregulation of polyamine metabolism has been implicated in numerous diseases, including neurodegenerative disorders, inflammatory conditions, autoimmune diseases, and cancer. This review provides an overview of pathophysiology of these conditions, highlighting polyamines’ role in immunometabolic alterations in the context of immune regulation.

Research Article Open Access

Upregulated Gene Expression of Histone Deacetylases (HDAC) 1, 2, and 11 in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

Samaneh Enayati, Mozhgan Moharamoghli, Ali Farazmand, Vahideh Hassan-Zadeh, Shiva Poursani, Elham Madreseh, Maryam Akhtari, Masoumeh Akhlaghi, Elham Farhadi, Asghar Hajiabbasi, Ahmadreza Jamshidi, Mahdi Mahmoudi

The histone deacetylase (HDAC) family consists of epigenetic modifiers that demonstrate anti-inflammatory activities, and hence they might have a substantial role in auto-inflammatory disorders including rheumatoid arthritis (RA). Therefore, the aim of this study is to investigate the expression of HDAC1, HDAC2, and HDAC11 genes in peripheral blood mononuclear cells (PBMCs) of RA cases compared to healthy controls.

Case Report Open Access

Clinical Case Report of CAR-T Therapy of Patient with Refractory Burkitt's Lymphoma

Tatiana Mikhailovna Doroshenko, Olga Alexandrovna Kalenik, Ihar Mikhalaevich Seviaryn, Kataryna Yureuna Zharkova, Denis Alexandrovich Davydov, Anna Sergeevna Portyanko, Alena Vladimirovna Sukalinskaya, Sergey Lvovich Polyakov, Natalia Eugenevna Konoplya

Approximately 20% of adult patients with Burkitt's lymphoma (BL) have relapsed/refractory disease, which is characterized by poor overall survival (OS) and virtually no therapeutic options after failure of two lines of chemotherapy, due in part to the peculiarities of tumor cell biology. Improved treatment strategies are an unmet need for these patients. There have been individual attempts to use chimeric antigen receptor (CAR)-T therapy in this patient population using anti-CD19, CD20, and CD22 cells.

Review Article Open Access

Chemokines and Their Receptors in Hepatitis B Virus Infection: A Comprehensive Review

Jiezuan Yang, Dan Cao, Ruiqi Tang, Xuefen Li

Chemokines, a group of small cytokines, play a central role in the pathogenesis of viral hepatitis by regulating the migration, proliferation, and activation of lymphocytes. These chemotactic factors of immune cells are directly involved in various cellular biological activities, including cell adhesion, angiogenesis, and diffusion. The aberrant expression of lymphocyte chemokines and their receptors is closely related to the biological behavior of host immune cells as well as the specific and non-specific immune responses to viral infections and may influence the prognosis of viral diseases.

Mini Review Open Access

Cytoreductive Nephrectomy Following Immunotherapy: Evolution, Pearls, and Pitfalls of Treatment

Laura E. Davis, Adam Calaway, Eric A. Singer, Shawn Dason

Renal Cell Carcinoma (RCC) is among the most frequently diagnosed malignancies in both genders with over 81,000 estimated cases in 2024. Despite increasing incidence of renal cell carcinomas <4 cm, up to 1/3 of patients diagnosed with RCC exhibit metastatic disease (mRCC) at time of diagnosis. Cytoreductive nephrectomy (CN), a procedure which encompasses the surgical removal of the primary tumor in patients with metastatic disease

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.

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.

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

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.

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

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.

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. 

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. 

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

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.

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. 

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.

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.

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.

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.

Commentary Open Access

The High Fat Diet Impacts the Plasticity between Fresh and Aged Neutrophils

Andrea Baragetti, Giuseppe Danilo Norata

Metabolic alterations induced by unhealthy lifestyles, including obesity and insulin resistance are often associated with increased innate immune response and chronic inflammation. Cholesterol has been identified as a key metabolite driving the activation of the inflammasome and the “epigenetic memory” in long-term living hematopoietic stem cells.  

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.

Commentary Open Access

Commentary on “Osteosarcoma from the Unknown to the Use of Exosomes as a Versatile and Dynamic Therapeutic Approach”

Ana Figueiras

This commentary mentions to our published article that intends to describe the properties that turn exosomes (Exo) into an efficient, as well as safe nanovesicle for drug delivery and treatment of osteosarcoma (OS). Nowadays, the results of conventional treatments are still unsatisfactory, mainly, in patients with recurrent disease or metastatic.

Review Article Open Access

Macrophages in Bone and Synovial Inflammation in Rheumatoid Arthritis

Mobina Jalalvand, Shaghayegh Khanmohammadi, Maryam Akhtari, Elham Farhadi, Ahmadreza Jamshidi, Mahdi Mahmoudi

Macrophages are members of the innate immune system; that originate from monocyte cells from the myeloid stem cells. In response to the tissue environment, monocytes differentiate into two subtypes of macrophages, M1, or M2. The M1 or classically activated macrophages (CAM) aggravate immune responses by releasing reactive oxygen species (ROS), and pro-inflammatory cytokines.

Review Article Open Access

Molecular Pathways in Sepsis Pathogenesis: Recent Advances and Therapeutic Avenues

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

Background: Sepsis remains a critical global health challenge with high mortality. This review summarizes current understanding of the intricate molecular mechanisms governing sepsis pathogenesis and highlights emerging therapeutic approaches.

Commentary Open Access

Role of Regulatory T cells in Prognosis, Diagnosis, and Treatment of Kidney Transplant Recipients

Katyayani Bejugama, Swarnalatha Guditi

The major issue in kidney transplantation remains the suppression of allograft rejection. Immunosuppressant decrease both donor-specific responsiveness and the risk of rejection in the months after transplantation and are maintained. The current immunosuppressant medications, although potent against short-time graft complications including acute renal rejection but are still less effective to ensure long-term graft survival.

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.

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

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

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

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.

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

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.

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

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]. 

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.

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.

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.

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

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.

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].

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

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

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).

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.

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.

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].

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.

Letter to the Editor Open Access

Is Omicron Variant of COVID-19 Threatening Health Like Other Variants?

Mousa Ghelichi-Ghojogh, Hamed Ghasemloo, Hamid Hosseinpour, Rohollah Valizadeh, Tella Sadighpour

World health organization (WHO) designated the variant B.1.1.529 a variant of concern, named Omicron, as a fastspreading SARS-CoV-2 variant, on 26 November 2021 which started from Southern Africa. In addition to the new mutations (more than 30 mutations in the spike protein), Omicron also carries mutations similar to the alpha, beta, gamma, and delta variants of coronavirus, and is collectively known as the fifth most disturbing variant.

Commentary Open Access

Vγ2⁺ γδ T Cells and Their Regulatory Potential in Skin Allograft Survival

Shilpi Giri, Girdhari Lal

Our recently published research article “Vγ2⁺ γδ T cells in the presence of anti-CD40L control surgical inflammation and promote skin allograft survival” revealed that the Vγ2⁺ subset of γδ T cells, which otherwise are known primarily for its proinflammatory function, regulate the survival of skin allografts in the presence of anti-CD40L.

Research Article Open Access

Preliminary Evidence of Differentially Induced Immune Responses by Microparticle-adsorbed LPS in Patients with Crohn’s Disease

P Ashwood

Inorganic microparticles are ubiquitous in the modern Western diet present as food additives and are actively scavenged by microfold (M) cells overlying human intestinal lymphoid aggregates. In Crohn’s disease (CD), inflammation is caused by the inability of the intestinal mucosa to sustain tolerance to gut luminal factors including bacteria and their by-products.

Review Open Access

Ubiquitin-Dependent Regulation of Treg Function and Plasticity

Yikui Li, Ping Wei, Fan Pan

Delicately, our immune system eliminates exogenous and endogenous threats and prevents harmful immune responses against the host. Regulatory T cells (Tregs) are indispensable in controlling immune responses and inducing immune tolerance; thus, immune homeostasis is maintained [1]. As a subset of CD4⁺ T cells, Tregs have been extensively studied for decades. They are best known for their ability to suppress immune responses, induce self-tolerance and help tumor cells escape immune surveillance [2-5]. Tregs mediate immune suppression via several mechanisms: They constitutively express cytotoxic T lymphocyte antigen-4 (CTLA-4), which competes with the costimulatory molecule CD28 for binding CD80/86 to downregulate T cell activation [6].

Commentary Open Access

The Importance of C5aR2 in Neutrophil Function and Its Impact on Neutrophil-mediated Diseases

Daniel Leonard Seiler, Marie Kleingarn, Syeda Zoela Gilani, Paula Emily Reichel, Jörg Köhl, Christian Marcel Karsten

C5aR2 serves as the second receptor for the anaphylatoxin C5a. It was identified about 10 years after identification of the first cognate receptor, C5aR1. Initially, C5aR2 was considered a mere decoy receptor for C5a. According to this view, its function was to scavenge excess C5a from C5aR1 and thereby exert anti-inflammatory effects. However, this initial view of C5aR2 had been oversimplified. 

Review Article Open Access

Going above and Beyond: Using an Attenuated Herpes Viral Vaccine Vector to Elicit Protective Immune Responses Through Neutralizing and Non-neutralizing Functions of Antibodies

Katherine E. Kaugars, Angelo R. Retamal-Diaz, Anna Paula de Oliveira, Pablo A. Gonzalez, William R. Jacobs Jr.

The COVID-19 pandemic has made the development of novel vaccines a high priority for public health. While many vaccines have focused on the generation of neutralizing antibodies, we have discovered a novel herpes simplex virus (HSV) vaccine candidate, designated ΔgD-2, that can preferentially elicit non-neutralizing antibodies that function through Fcγ receptor (FcγR) activation

Research Article Open Access

Establishment of an Indirect Enzyme-linked Immunosorbent Assay for Detection of the NS4 Protein of Bluetongue Virus

Ji Ma, Xianping Ma, Rang Wang, Fang Li, Tingjun Hu, Huashan Yi

An indirect enzyme-linked immunosorbent assay (iELISA) was established to detect the serological prevalence of bluetongue virus (BTV) infection in ruminant populations. A recombinant NS4 (rNS4) protein was used as the encapsulated antigen. Optimization of the iELISA included the encapsulated antigen, serum dilution, blocking solution, and working concentration of a horseradish peroxidase (HRP)-labeled secondary antibody (Ab) by the square-matrix titration test.

Mini Review Open Access

Profiling Proteasome Activities in Peripheral Blood – A Novel Biomarker Approach

Laylan Bramasole, Silke Meiners

The proteasome system in the cell degrades the majority of intracellular proteins. The broad nature of its substrates makes proteasome activity crucial for many cellular functions, such as protein quality control, transcription, apoptosis, immune responses, cell signaling and differentiation. The proteasome system is thus an effective therapeutic target for malignant and non-malignant diseases. In this mini-review, we would like to highlight that proteasome function has also the potential to serve as a biomarker for disease severity and response to treatment. This notion is based on the observation that the six catalytic sites of the proteasome are distinctly altered in peripheral immune cells of patients with chronic inflammatory and autoimmune diseases

Commentary Open Access

The Issue of Monocyte Activation in ASD: Troubles with Translation

P Ashwood, R.J. Moreno

Autism spectrum disorder (ASD) prevalence has increased year on year for the past two decades and currently affects 1 in 44 individuals in the US. An increasing number of studies have pointed to increased immune activation as both an etiological agent and also involved in the ongoing pathological process of ASD. Both adaptive and innate immune responses have been implicated. Evidence of innate dysregulation has so far included increased production of innate inflammatory cytokines, increased cell numbers, and altered activation in monocytes in the blood and microglia in the brain.

Research Article Open Access

Sialyllactose Prevents Cartilage Damages via M0 Macrophage Maintenance in Yucatan Mini-Pig Osteoarthritis Model

Kyung-Tai Kim, Young-Kyu Kim, Mi-Jin Yang, Min-Young Kim, Lila Kim, Jeong Ho Hwang

Sialyllactose, known to be abundant in human breast milk, has anti-inflammatory properties, but its preventive effect on osteoarthritis remain unclear. Here, we demonstrated the efficacy of 3’ sialyllactose (3’ SL) and 6’ sialyllactose (6’ SL) in preventing osteoarthritis in Yucatan mini-pigs. Twelve female Yucatan mini-pigs were administered 0, 200, 400 mg 3’ SL or a combination of 200 mg 3’ SL + 200 mg 6’ SL for 12 weeks (4weeks before and 8 weeks after surgery); then, osteoarthritis was induced in the left knee by anterior cruciate ligament transection surgery. Kinematic variables were used to quantify gait analysis on the treadmill, and the degree of osteoarthritis was analyzed in the femur and tibia cartilage

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

Adaptive immunity relies on an efficient lymphocyte response, enabling an organism to defend itself against infections or malignancies. Lymphocyte repertoire may be impacted by various factors, including conditions such as primary immune deficiencies or Acquired Immunodeficiency Syndrome (AIDS), or by treatments such as chemotherapy.

Commentary Open Access

Rethinking Radiation Dose-Fractionation in the Immuno- Oncology Era

Joseph Sia, Nicole M. Haynes

Radiation therapy (RT) is a highly sophisticated and effective cancer treatment modality that is of central importance in modern oncology. It is estimated that RT contributes to 40% of all cancer cures and at least 1 in 2 cancer patients would benefit from RT during their course of illness [1,2].

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 .

Short Communication Open Access

Microbial Resistance to Photodynamic Therapy

Alison M Mackay

Microbial resistance to antibiotics has become a major area of research given that it caused 1.27 million human deaths in 2019. Methicillin-resistant staphylococcus aureus (MRSA) accounted for half these deaths, and lower respiratory infection is the most burdensome syndrome. 

Commentary Open Access

Joint Health Markers in Hemophilia: The State of the Art

E.D.P. van Bergen, S.C. Mastbergen, F.P.J.G. Lafeber, R.E.G. Schutgens, L.F.D. van Vulpen

Hemophilia is a rare congenital bleeding disorder caused by a lack of or diminished activity of clotting factor VIII (hemophilia A) or IX (hemophilia B). This deficiency leads to an increase in spontaneous and traumatic bleeding especially in the large hinged joints.

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

Aging is accompanied by numerous changes that affect almost all components of the immune system, collectively called immunosenescence. Immunosenescence has long been considered detrimental because it is often accompanied by the subclinical accumulation of pro-inflammatory factors and inflammation. Together, it is suggested that immunosenescence and inflammation are at the origin of most diseases of the elderly, such as infections, cancer, autoimmune disorders and chronic inflammatory diseases. However, a large number of immunogerontologists have changed this negative interpretation of immunosenescence regarding its significance in age-related alterations of the immune system. Considering these changes from an evolutionary perspective, it is preferable to view it as adaptive or remodeling. Although it is conceivable that global immune changes can lead to various diseases, it is also obvious that these changes are necessary for extended survival or longevity.

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

FLIP-expressing myeloid cells as driver of systemic immune disorders

Alberto Atanasio, Davide Rizzini, Stefano Ugel

Cellular and viral FLICE (FADD-like IL-1β-converting enzyme)- inhibitory proteins (c-FLIP and vFLIP respectively) are traditionally recognized for their relevance in the anti-apoptotic activity, regulating cell survival and proliferation by inhibiting caspase-mediated cell death.

Review Article Open Access

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

Jens C. Kleiner, Christian F. Krebs

Focusing on adaptive immunity there is a humoral and a cellular immune response. The humoral response is executed by antibodies acting via antigen specific binding. These antibodies are produced by activated B-lymphocytes in order to bind and neutralize antigens.

Commentary Open Access

The Potential of Combination Therapies and Patient Stratification to Improve CCR₂ Inhibition Therapeutics

Jason E. Duex, Dan Theodorescu

Chemokines and their receptors are the communication mechanism used by cells of the immune system, allowing them to identify and eliminate pathogens and cancerous cells. However, it is becoming clear that chemokines and their receptors are also playing a role in tumor progression and metastasis.

Research Article Open Access

Human Gray and White Matter Metabolomics to Differentiate APOE and Stage Dependent Changes in Alzheimer’s Disease

Tyler C. Hammond, Xin Xing, Lucy M. Yanckello, Arnold Stromberg, Ya-Hsuan Chang, Peter T. Nelson, Ai-Ling Lin

Alzheimer’s disease (AD) is a leading cause of death and morbidity in the United States [1]. The hallmarks of AD are β-amyloid (Aβ) and tau. However, studies have indicated that metabolic dysfunction may play a more pivotal role in the progression of AD [2]. Glucose hypometabolism and mitochondrial dysfunction are well-known features of AD [2].

Commentary Open Access

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

Hong Xin

Disseminated candidiasis is the leading cause of lifethreatening fungal infections in humans. This is especially the case in immunocompromised individuals, and in hospitalized patients including intensive care unit patients. 

Commentary Open Access

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

Peiling Huang MM, Weijun Gong MD

Recently researchers have focused on the role of neuroinflammation in neurodegenerative diseases such as Alzheimer’s disease, atrophic lateral sclerosis, Huntington’s disease, Multiple sclerosis and Parkinson’s disease (PD). PD is one of the leading neurodegenerative diseases in developed countries and the complete etiological scenario remains unknown. A-synuclein misfolding and aggregation, mitochondrial dysfunction, dysfunctional protein clearance and ubiquitin/proteasome systems, and neuroinflammation have been associated with PD.

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

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.

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.

Commentary Open Access

Commentary on “A Vaccine for Photodynamic Immunogenic Cell Death: Tumor Cell Caged b y Cellular Disulfide–Thiol Exchange for Immunotherapy”

Jie Zang, Haiqing Dong

Tumor immunotherapy, including monoclonal antibody of immune checkpoint blockade, therapeutic antibody, cancer vaccine and cell therapy, etc., is to restart and maintain the tumor immune cycle, restore the normal antitumor immune response of the body, so as to control and eliminate the tumor.

Commentary Open Access

Targeting Ovarian Cancer with IL-2 Cytokine/Antibody Complexes: A Summary and Recent Advances

Yilun Deng, Ryan M Reyes, Chenghao Zhang, José Conejo-Garcia, Tyler J. Curiel

Interleukin (IL)-2 was first identified as a potent T cell growth factor in 1976 [1] and cloned in 1983 [2]. In the late 1990s, IL-2 gained further attention as the first immunotherapy demonstrating clinical efficacy against metastatic cancer, as high dose IL-2 was approved by the United States Food & Drug Administration (FDA) for the treatment of metastatic renal cell carcinoma in 1992 and metastatic melanoma in 1998.

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. 

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

Mutations in ELANE, the gene for neutrophil elastase (NE), are the most common cause of cyclic and severe congenital neutropenia

Review Article Open Access

Neurological Manifestations Associated with SARS-CoV-2 Invasion of the Autonomous Nervous System

Erwan Poivet, Matthieu Daniel, Fernando A. Bozza, Tarek Sharshar, Pierre-Marie Lledo

COVID-19 patients can develop various central neurological disorders, including loss of smell and taste (anosmia and ageusia, respectively), ischemic injury (stroke), encephalopathy (delirium), and encephalitis, but also peripheral damages such as Guillain-Barré Syndrome (GBS).

Commentary Open Access

Application of Mucosal Immune-related Molecular Adjuvants CCL19 and CCL28 in Enhancing the Function of HSV-2 gD DNA Vaccine

Yan Yan, Xu Wang, Renfang Chen

Herpes simplex virus type 2 (HSV-2) develops an annual incidence of 2.3 million people worldwide, which can lead to life-long latent infections, asymptomatic and reactivations [1,2], and with occasional symptomatic episodes causing ulcerative lesions in the genitalia and naus.

Research Article Open Access

Sleep Disturbances are a Significant Predictor of Chikungunya Arthritis Flare Severity

Sarah Renee Tritsch, Richard Amdur, Liliana Encinales, Andres Cadena Bonfanti, Paige Fierbaugh, Geraldine Avendaño, Carlos Andres Herrera Gomez, Karol Suchowiecki, Evelyn Mendoza-Torres, Wendy Rosales, Dennys Jimenez, Carlos Alberto Perez Hernandez, Alfonso Sucerquia Hernández, Paula Bruges Silvera, Yerlenis Galvis Crespo, Alberto David Cabana Jimenez, Jennifer Carolina Martinez Zapata, Christopher N. Mores, Gary Steven Firestein, Gary Leonard Simon, Aileen Yu-hen Chang

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that causes debilitating arthritis. In a cohort of 500 Colombian patients, one quarter reported joint pain 20 months after infection, and further, 1 out of 8 had joint pain three years after infection.

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.

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

Approximately 1.6-3.8 million people sustain a mild traumatic brain injury (mTBI) in the US annually. This amounts to the hospitalization of 100-300 per 100,000 young adults. The Centers for Disease Control and Prevention reports that around 5.3 million people live with a permanent disability after mTBI, and there are currently no known restorative therapies.

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 [1]. 

Commentary Open Access

Proteome-wide Epitope Prediction: Leveraging Bioinformatic Technologies in Rational Vaccine Design

Lindsay M.W. Piel, Stephen N. White

Vaccine development began in the 1790’s when Edward Jenner used cowpox to confer protection against the smallpox virus. The field of vaccinology has greatly expanded since then, wherein vaccination has been a valuable tool in the decline of many diseases.

Research Article Open Access

Expression of Pu.1, C/Ebpα and Bach₁ Transcription in Immune Cells in Patients with Cancer

Gulnur K. Zakiryanova, Elena Kustova, Nataliya T. Urazalieva, Emile T. Baimukhametov, Valeriy A. Makarov, Galina V. Shurin, Narymzhan N. Nakisbekov, Michael R. Shurin

Cancer remains one of the leading causes of death worldwide despite a significant progress in cancer diagnostics, treatment and prophylactics during last decades. It is generally accepted that the development and progression of cancer are closely associated with dysregulated functioning and diminishing of local and systemic immune responsiveness.

Commentary Open Access

The Return of Tocilizumab for Patients with COVID-19 Pneumonia

Kathy Tin, DO, Annamarie Fernandes, MD, Roderick Go, DO

The COVID-19 pandemic has now impacted the global population for over a year. It has been devastating for many and has challenged us all in many ways. While the advent of vaccinations looks to curtail the number of cases, multiple challenges to ending the pandemic remain, including the advent of variants, vaccine hesitancy, access to vaccines, and the impaired efficacy of vaccines in immunocompromised persons. Thus, it is still essential to continue investigating treatments for COVID-19.

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.

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 [1].

Commentary Open Access

Novel Combination Treatments for AML

Montserrat Estruch, Camilla Vittori, Teresa Muñoz-Montesinos, Kristian Reckzeh, Kim Theilgaard-Mönch

Drug resistance of cancer patients toward chemotherapy remains a major problem in the clinic. Hence, understanding the intrinsic and acquired molecular mechanisms of drug resistance in cancer patients is paramount to identify relevant targets for therapeutic interventions that enhance chemotherapy response, and ultimately improve clinical outcome.

Research Article Open Access

The Variable Immune Response to SARS-CoV-2 Infection and Potential Treatment with Combination IL-15 and IL-21

Stephen William Wilz

SARS-Cov-2 is the virus that causes the disease COVID-19. The disease has led to the worst worldwide health crisis in 100 years. While many patients remain asymptomatic, most patients develop a mild respiratory infection. Symptoms include cough, fever and chills, fatigue and body aches, headache and loss of the sense of taste or

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

In healthy individuals, Staphylococcus aureus (S. aureus) can be found commensally in sebaceous sites in the skin microbiome [1].

Commentary Open Access

Body Mass Index and COVID-19: Likely Causes for Obesity and Undernutrition Correlation with Disease Severity

Nicolas Vitale

Coronaviruses are one of the viruses causing the common cold, a disease that has never had a cure nor any effective prevention. They form are a large family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates, and for which bats are believed to be an important reservoir.

Review Article Open Access

Resilience in Rheumatic and Musculoskeletal Diseases

Robert Passier, Federica Maggi, Francesca Romana Spinelli, Cristina Iannuccelli, Fabrizio Conti

Along the last decade, likewise in other fields, the concept of resilience has been gaining relevance in medicine and psychology where, although many different definitions have been proposed, it can be briefly described as the skill to positively cope with stressful life events [1]. 

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

Colorectal cancer (CRC) is the third most common cause of cancer related death worldwide. Its outcome depends on different factors. On one hand there are cancer related features, including mutations, microsatellite status, and methylation alterations.

Commentary Open Access

Immune Cells and Transcriptional Signatures Revealed Novel Regulators and Predict Clinical Response to Biologic Therapy in Ulcerative Colitis

Suzana D. Savkovic

Inflammatory Bowel Disease (IBD), which includes Crohn’s Disease (CD) and Ulcerative Colitis (UC), has a heterogeneous pathogenesis underlined by genetic predisposition, intestinal barrier dysfunction, impaired immune response, and microbiota imbalance [1-3]

Review Article Open Access

Megalin-Mediated Trafficking of Mitochondrial Intracrines: Relevance to Signaling and Metabolism

David Sheikh-Hamad, Michael Holliday, Qingtian Li

Low-molecular weight proteins, cofactors, amino acids, metabolites and many bioactive signaling molecules are filtered through the glomeruli. Evolution has yielded highly conserved pathways in proximal tubule epithelium for the reabsorption of filtered molecules;

Review Article Open Access

Immunotherapy for Dogs: Still Running Behind Humans

Hans Klingemann

Back in 2017, I published a review on the immunotherapy options for dogs with cancer. Somewhat provocatively the paper was entitled: Immunotherapy for dogs: Running behind humans. 

Commentary Open Access

Murine Models of Alcohol Consumption: Imperfect but Still Potential Source of Novel Biomarkers and Therapeutic Drug Discovery for Alcoholic Liver Disease

Khaled Alharshawi, Costica Aloman

Improving our knowledge regarding the cellular and molecular mechanisms underlying murine models of alcoholic liver injury should enhance the management and therapies of alcoholic liver disease (ALD) seen in humans [1]. Although none of the animal models available reproduce all main aspects of human ALD, they still provide very

Mini Review Open Access

Glycogen Synthase Kinase-3 (GSK-3) Regulation of Inhibitory Coreceptor Expression in T-cell Immunity

Mark E. Issa, Christopher E. Rudd

While the immune system is capable of recognizing tumor antigens, certain cancer cells evade immune detection and destruction [1].

Review Article Open Access

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

Junfei Zhao, Raul Rabadan, Arnold J. Levine

By the 1960’s there were a number of suggestions that the immune system played a role in detecting and rejecting cancerous cells. The next thirty to forty years saw a large number of attempts to identify the antigens found in a tumor that could lead to tumor rejection.

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

The COVID-19 pandemic has placed unprecedented strains on our medical system as specialties have had to reconsider “essential” in-person services and find novel ways to remotely ensure continuity of care. One such modality of care includes telehealth services, which have experienced a rapid rise in utility with a reported 4,347% increase in telehealth visits from March 2019 to March 2020 [1].

Short Communication Open Access

Increased Binding Affinity of Furin to D614G Mutant S-glycoprotein May Augment Infectivity of the Predominating SARS-CoV-2 Variant

Sardar Sindhu, Rasheed Ahmad, Fahd Al-Mulla

The coronavirus disease (COVID)-19 pandemic has profoundly devastated human health and wellbeing all over the world, along with colossal setback to global economy in terms of soaring new infections, hospitalizations, ICU admissions, work losses, closures of businesses and institutions, bankruptcies, and precautionary measures

Commentary Open Access

Using Immune Cell/Adipocyte Co-Culture Models to Identify Inflammatory Paracrine Signaling Mechanisms: A Process Attenuated by Long-Chain N-3 Polyunsaturated Fatty Acids

Jennifer M. Monk, Amber L. Hutchinson, Jamie L.A. Martin, Lindsay E. Robinson

This invited Commentary is on the methods paper entitled “Studying adipocyte and immune cell cross talk using a co-culture system” in Immunometabolism: 

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

Role of Perforin-2 in Regulating Type I Interferon Signaling

Gregory V Plano, Noula Shembade

Type I interferons (IFNs) produced in response to infections with either bacterial, viral or fungal pathogens are critical to induce antimicrobial defenses in infected and adjacent cells to reduce the spread of microbes, initiate communication between innate and adaptive immunity, and to promote the survival of the host [1]. Improper induction or regulation of type I IFN signaling can lead to chronic infection-induced inflammation-related diseases, including septic shock, autoimmune diseases, and inflammatory syndromes [2].

Commentary Open Access

Guanylate Binding Proteins promote anti-Leishmania Host Cell Defense

Arun Kumar Haldar

Leishmania donovani is an obligatory intracellular protozoa pathogen that transmits by sand flies to mammalian hosts. L. donovani is the causative agent of the disease Visceral Leishmaniasis (VL), also known as Kala-azar, which causes hepatosplenomegaly i.e., enlargement of the spleen and liver in 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) [1]. 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 [2].

Commentary Open Access

Unconventional Approaches to Direct Detection of Borreliosis and Other Tick Borne Illnesses: A Path Forward

Lance Liotta, Alessandra Luchini

The current COVID-19 pandemic has brought to public attention the conceptual difference between a test for COVID-19 derived RNA or proteins indicating the presence of an active infection, versus COVID-19 serology testing indicating pathogen infection. Only the former test for molecules derived from COVID-19 provides reliable

Commentary Open Access

COVID-19 Clinical Outcomes and Vaccine Efficacy among Patients with Hematologic Malignancies

Sarah Gillaspie, Marc S Hoffmann

The coronavirus disease 2019 (COVID-19) pandemic places the treating hematologist in a quandary: how best to protect patients with hematologic malignancies from potentially deadly COVID-19 infection while also providing the best therapy for their disease and maximizing opportunities for cure.

Commentary Open Access

M1 Macrophages are More Susceptible to Necroptosis

Qin Hao, Steven Idell, Hua Tang

Macrophages are important cells of the innate immune system and play a crucial role in host immune defense against infection and injury [1-3]. Macrophages form the first line of defense against airborne particles and microbes through multiple functions including phagocytosis, production of cytokines and chemokines, and antigen presentation.

Review Article Open Access

The Role of Myeloid Populations during Perinatal Liver Injury and Repair

Anas Alkhani, Sarah Mohamedaly, Amar Nijagal

The maturation of the immune system is a complex process that undergoes major transitions during fetal and neonatal development [1]. Throughout this developmental window, the response to liver injury is dependent on the nature and timing of the insult [2].

Commentary Open Access

Duration of SARS-CoV-2 Infectivity

Seitz Tamara, Kelani Hasan, Wenisch Christoph, Laferl Hermann

The ongoing SARS-CoV-2 pandemic led to a high number of deaths worldwide as well as an overload of healthcare systems and an economic collapse. One of the reasons can be attributed to the lack of knowledge about the duration of infectivity at the beginning of the pandemic, resulting in hospital isolation of patients and

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

Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma

Katherine E. Masih, Jun S. Wei, David Milewski, Javed Khan