Journal of Immunology

J Immunol. 2026 Aug 29;215(9):vkag247. doi: 10.1093/jimmun/vkag247. ABSTRACT SWI/SNF chromatin remodeling complexes regulate gene expression during development and differentiation. These complexes exist in distinct forms, including the polybromo-associated BAF (PBAF) complex, defined by the ARID2 subunit. ARID2 is frequently mutated in B cell leukemias, but its role in normal B cell development remains unknown. Using … Read more

J Immunol. 2026 Aug 29;215(9):vkag179. doi: 10.1093/jimmun/vkag179. ABSTRACT Psoriasis is a chronic inflammatory skin disease involving intricate neuroimmune crosstalk. However, the specific mechanisms and therapeutic targets remain elusive. In this study, a pilot clinical trial demonstrated that intravenous scopolamine, a muscarinic receptor antagonist, significantly ameliorated skin lesions in psoriasis patients. Consistently, scopolamine reduced inflammation in … Read more

J Immunol. 2026 Aug 29;215(9):vkag233. doi: 10.1093/jimmun/vkag233. ABSTRACT Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting at least 2% of the global population. Papaverine, an alkaloid with known anti-inflammatory, anti-cancer, and RAGE-antagonistic properties, has not been previously evaluated for anti-psoriatic activity. This study investigated the protective effects and mechanisms of papaverine in an imiquimod … Read more

J Immunol. 2026 Aug 29;215(9):vkag241. doi: 10.1093/jimmun/vkag241. ABSTRACT The role of selenium in tumor progression remains controversial, and its mechanisms of action in the context of immunotherapy are poorly understood. In this study, our findings indicate that selenium supplementation did not alter immune parameters, induce organ damage under healthy conditions, or affect the growth of … Read more

J Immunol. 2026 Aug 29;215(9):vkag244. doi: 10.1093/jimmun/vkag244. ABSTRACT The increasing demand for nuclear power and radiotherapy has expanded potential avenues for human exposure to whole-body irradiation (WBI), underscoring the need to understand its impact on immune cells. While prior studies have explored radiation-induced disruptions in immune homeostasis, the direct effect of WBI on pre-existing memory … Read more

J Immunol. 2026 Aug 29;215(9):vkag238. doi: 10.1093/jimmun/vkag238. ABSTRACT Many autoimmune diseases exhibit a female sex bias in prevalence and severity, yet the mechanisms for this remain unclear. 17β-estradiol (E2) is a steroid sex hormone with established immunomodulatory roles in CD4+ T cells, which express the nuclear estrogen receptors ERα and ERβ. Autoimmune disease patients exhibit … Read more

J Immunol. 2026 Aug 29;215(9):vkag224. doi: 10.1093/jimmun/vkag224. ABSTRACT Hepatic ischemia-reperfusion (I/R) injury triggers release of small extracellular vesicles (sEVs) that can function as systemic conveyors of inflammatory signals. While sEV-mediated immune cell modulation has been studied extensively in vitro, knowledge is based largely on sEVs derived from cultured cells, rather than injured tissues. Consequently, the … Read more

J Immunol. 2026 Aug 29;215(9):vkag178. doi: 10.1093/jimmun/vkag178. ABSTRACT Neutrophils have been implicated in mediating immune crosstalk between injured tissue and distal organs, either promoting local and distal inflammation or mediating tissue repair. Skin injury from ultraviolet (UV) light triggers neutrophil migration to the kidney, which may have implications for nephritis flares in systemic lupus erythematosus. … Read more

J Immunol. 2026 Aug 29;215(9):vkag237. doi: 10.1093/jimmun/vkag237. ABSTRACT Through screening of a VHH phage display library constructed from an alpaca immunized with the recombinantly expressed murine myelin oligodendrocyte (MOG)-specific 2D2 T cell receptor (TCR), we identified nanobodies that reduced antigen-driven 2D2 T cell activation in vitro. Immunoblotting and staining confirmed TCRβ chain reactivity and Vβ11-associated … Read more

J Immunol. 2026 Aug 4;215(8):vkag199. doi: 10.1093/jimmun/vkag199. ABSTRACT Invariant natural killer T (iNKT) cells are unconventional ɑβ T cells that respond to lipid-based antigens. They play a vital role in response to infections and are involved in diseases such as allergic asthma and cancer. Despite clear immunological roles across multiple diseases, remarkably few tools exist … Read more

J Immunol. 2026 Aug 4;215(8):vkag235. doi: 10.1093/jimmun/vkag235. ABSTRACT SARS-CoV-2 has continued to evolve over time, necessitating the adaptation of vaccines to maintain efficacy. Monoclonal antibodies (mAbs) against SARS-CoV-2 were a key line of defense for unvaccinated or immunocompromised individuals. However, these mAbs are now ineffective against current SARS-CoV-2 variants. Here, we tested 3 aspects of … Read more

J Immunol. 2026 Aug 4;215(8):vkag201. doi: 10.1093/jimmun/vkag201. ABSTRACT The invariant chain (Ii) trimerizes in the endoplasmic reticulum and swiftly associates with nascent alpha and beta chains of major histocompatibility complex class II (MHCII) molecules. Ii was ascribed many roles pertaining to the antigen presentation capacity of MHCII molecules. The lack of Ii in knockout mice … Read more

J Immunol. 2026 Aug 4;215(8):vkag223. doi: 10.1093/jimmun/vkag223. ABSTRACT Neuropathic pain (NP) is a refractory clinical disorder in which microglial pyroptosis plays a crucial role, yet the epigenetic regulation by lysine demethylase 4A (KDM4A) remains unclear. In this study, chronic constriction injury (CCI) rat models were established, and KDM4A was knocked down to evaluate its effects … Read more

J Immunol. 2026 Aug 4;215(8):vkag214. doi: 10.1093/jimmun/vkag214. ABSTRACT The human T cell receptor (TCR) repertoire is generated in the thymus through a process of recombination involving two gene loci, TRA and TRB, and the pairing of the resulting peptide chains. Because of the lack of allelic exclusion in TRA loci, it is possible for a … Read more

J Immunol. 2026 Aug 4;215(8):vkag213. doi: 10.1093/jimmun/vkag213. ABSTRACT The complex and sophisticated sea urchin innate immune system relies on conserved immune receptor and effector molecules plus the euechinoid-specific Transformer family. Native SpTransformer (natSpTrf) proteins in Strongylocentrotus purpuratus respond to immune challenge by augmenting phagocytosis of microbes. These proteins show significant sequence diversity both within and … Read more

J Immunol. 2026 Aug 4;215(8):vkag229. doi: 10.1093/jimmun/vkag229. ABSTRACT CD4+ T cell dysfunction plays a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the expression, phenotypic characteristics, and potential clinical significance of CD55, a membrane-bound complement regulatory protein, in peripheral blood CD4+ T cells from RA patients. Flow cytometric analysis … Read more

J Immunol. 2026 Aug 4;215(8):vkag236. doi: 10.1093/jimmun/vkag236. ABSTRACT The programmed death ligand 1/programmed cell death 1 (PD-L1/PD-1) serves as a critical immune checkpoint in T cell-mediated immune responses, playing a central role in maintaining peripheral immune tolerance and homeostasis. Although early vertebrates lack a PD-1 homolog and they retain PD-L1, the functional significance and regulatory … Read more

J Immunol. 2026 Aug 4;215(8):vkag191. doi: 10.1093/jimmun/vkag191. ABSTRACT Metastatic disease is the prime cause of death from many malignancies. Due to the multiple different lesions and the increased aggressiveness of the cancer cells, metastatic disease is often difficult to treat. Here, the introduction of immune checkpoint blockers (ICBs) has greatly helped to improve patients’ prognosis … Read more

J Immunol. 2026 Aug 4;215(8):vkag231. doi: 10.1093/jimmun/vkag231. ABSTRACT Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense. Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype-specific gene regulation are largely unaddressed. Here, we performed an integrated multiomics analysis (RNA sequencing, … Read more

J Immunol. 2026 Aug 4;215(8):vkag152. doi: 10.1093/jimmun/vkag152. ABSTRACT The gastrointestinal pathogen Clostridioides difficile is a major burden for health systems due to high rates of recurrence. C. difficile pathogenesis is mediated by two virulence factors, toxin A (TcdA) and toxin B (TcdB). Antibodies specific for TcdA and TcdB are correlated with protection from symptomatic recurrence; … Read more

J Immunol. 2026 Aug 4;215(8):vkag207. doi: 10.1093/jimmun/vkag207. ABSTRACT Sex differences exist in the immune responses to infections and in the prevalence and severity of autoimmune and allergic diseases. These sex differences may be caused by sex hormones and/or variable inactivation of X chromosome genes. The 4 core genotypes mice allow for distinction between the effects … Read more

J Immunol. 2026 Aug 4;215(8):vkag220. doi: 10.1093/jimmun/vkag220. ABSTRACT Little is known about the role of semaphorin 3E (Sema3E) in B cell responses and immunoglobulin regulation. Our recent data indicate that Sema3e knockout mice have significantly higher serum levels of total and allergen-specific IgE in allergic asthma, suggesting Sema3E’s crucial role in modulating the humoral response. … Read more

J Immunol. 2026 Aug 4;215(8):vkag219. doi: 10.1093/jimmun/vkag219. ABSTRACT Systemic sclerosis (SSc) is an autoimmune condition affecting several organs. It is identified by thickening of the dermis, connective tissue affected by collagen accumulation, and vascular injuries that induce hypoxia. The present study aimed to determine whether extracellular vesicles (EVs) from adipose-derived stem cells (ADSCs) attenuated bleomycin-induced … Read more

J Immunol. 2026 Aug 4;215(8):vkag228. doi: 10.1093/jimmun/vkag228. ABSTRACT Sepsis-induced cardiac dysfunction is a primary contributor to mortality, and microRNAs (miRNAs) are recognized as crucial mediators in sepsis pathogenesis. This study aims to identify the key regulatory miRNAs involved in cardiac dysfunction stemming from sepsis. We developed a rat model of sepsis using cecal ligation and … Read more

J Immunol. 2026 Aug 4;215(8):vkag198. doi: 10.1093/jimmun/vkag198. ABSTRACT Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with murine cDC1s, generated in culture from bone marrow cells … Read more

J Immunol. 2026 Aug 4;215(8):vkag212. doi: 10.1093/jimmun/vkag212. ABSTRACT Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that recognizes bacterial-derived antigens presented on MR1. Upon TCR triggering, MAIT cells respond rapidly, producing a range of effector molecules which facilitate host-protective responses in the context of microbial infections. In contrast, MAIT cell responses … Read more

J Immunol. 2026 Aug 4;215(8):vkag200. doi: 10.1093/jimmun/vkag200. ABSTRACT Lysosomes drive antigen proteolysis and peptide loading for major histocompatibility complex class II (MHCII) presentation in antigen-presenting cells (APCs), enabling activation of peptide-specific CD4+ T helper cells (CD4+ Th cells). Tight regulation of endocytic trafficking, protease activity, and peptide editing is required to generate stable peptide-MHCII complexes … Read more

J Immunol. 2026 Aug 4;215(8):vkag209. doi: 10.1093/jimmun/vkag209. ABSTRACT In the established model of classical trained immunity, metabolic and epigenetic hubs serve as central integrators of innate memory. While typically associated with proinflammatory reprogramming, the regulation of autophagy and cellular proteostasis remains essential for guiding macrophage differentiation and ensuring efficient pathogen clearance without excessive inflammation. In … Read more

J Immunol. 2026 Aug 4;215(8):vkag221. doi: 10.1093/jimmun/vkag221. NO ABSTRACT PMID:42580673 | DOI:10.1093/jimmun/vkag221

J Immunol. 2026 Aug 4;215(8):vkag216. doi: 10.1093/jimmun/vkag216. ABSTRACT Healthy aging relies on the maintenance of a diverse T cell pool. This diversity is ensured by balancing thymic output, differentiation of naive into memory T cells, T cell proliferation and cell death. For naive T cells, the balance of these processes differs between standard laboratory mice … Read more

J Immunol. 2026 Aug 4;215(8):vkag230. doi: 10.1093/jimmun/vkag230. ABSTRACT Osteoarthritis (OA), the most prevalent degenerative joint disease, leads to significant disability in the elderly and is characterized by functional and structural deterioration of the knee joint. This study aimed to investigate the therapeutic potential of skullcapflavone II (SkII), a flavonoid known for its anti-inflammatory properties, in … Read more

J Immunol. 2026 Aug 4;215(8):vkag227. doi: 10.1093/jimmun/vkag227. ABSTRACT B-cell responses rely on a tightly coordinated interplay between transcriptional programs and metabolic reprogramming. Upon activation, B cells remodel their metabolic profiles, with enhanced glutamine metabolism supporting biomass synthesis and proliferation. However, whether and how glutaminolysis underpins B-cell responses in early vertebrates remains largely unexplored. Here, using … Read more

J Immunol. 2026 Aug 4;215(8):vkag222. doi: 10.1093/jimmun/vkag222. ABSTRACT The immune system initially protects hosts against viral pathogens, with chemokines guiding immune cell movement. However, their expression patterns and immune cell recruitment mechanisms during transmissible gastroenteritis virus (TGEV) infection are still not fully understood. Here, we identified a distinct chemokine expression profile in intestinal epithelial cells … Read more

J Immunol. 2026 Aug 4;215(8):vkag218. doi: 10.1093/jimmun/vkag218. ABSTRACT Golden hamster (Mesocricetus auratus) and ferret (Mustela putorius furo) are important animal models in studies of human infectious disease. They are used widely to investigate pathogen-spreading mechanisms and host immunology to evaluate the safety and efficacy of small molecules, biologic drugs and vaccines. To this end, immunoglobulin … Read more

J Immunol. 2026 Aug 4;215(8):vkag226. doi: 10.1093/jimmun/vkag226. ABSTRACT CCR2+ monocytes are recruited to sites of acute myocardial injury, where they play a critical role in clearing necrotic debris and replenishing the depleted resident macrophage population. Although this response is necessary for early tissue repair, prolonged activation of inflammatory pathways and persistent recruitment of CCR2+ monocytes … Read more

J Immunol. 2026 Aug 4;215(8):vkag189. doi: 10.1093/jimmun/vkag189. ABSTRACT COVID-19 continues to present ongoing global health challenges driven by diverse immune responses and heterogeneous clinical outcomes. The ACCORD trial evaluated 3 investigational treatments-bemcentinib, tozorakimab, and zilucoplan-in patients hospitalized with COVID-19, each of which has demonstrated clinical efficacy. To better understand their molecular mechanisms, we conducted a … Read more

J Immunol. 2026 Aug 4;215(8):vkag217. doi: 10.1093/jimmun/vkag217. ABSTRACT Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, yet the host pathways that regulate antigen presentation and lung inflammation during Mycobacterium tuberculosis (Mtb) infection are incompletely defined. Sorting nexin 5 (SNX5) is a protein implicated in endosomal trafficking, antigen … Read more

J Immunol. 2026 Aug 4;215(8):vkag206. doi: 10.1093/jimmun/vkag206. ABSTRACT There is substantial interest in developing novel engineering strategies to promote the sustained metabolic fitness of therapeutic T cells. We previously showed that overexpression of RAS homologue enriched in brain (RHEB), a positive regulator of mammalian target of rapamycin complex 1 (mTORC1), promotes aerobic glycolysis and increases … Read more

J Immunol. 2026 Aug 4;215(8):vkag215. doi: 10.1093/jimmun/vkag215. ABSTRACT Adenine-thymine (AT)-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) that post-transcriptionally stabilizes mRNAs encoding proinflammatory mediators, including Interleukin-6 (IL-6), thereby amplifying inflammation. However, structural basis and regulatory mechanisms of Arid5a function remain poorly defined. In this study, we identified and characterized a conserved allosteric … Read more

J Immunol. 2026 Aug 4;215(8):vkag166. doi: 10.1093/jimmun/vkag166. ABSTRACT Cancer patient-derived T cells often exhibit impaired activation and functional responsiveness due to chronic antigen exposure and therapy-induced immune dysregulation, limiting the efficacy of current immunotherapies. Mechanical forces, such as fluid shear stress (FSS), are emerging as critical regulators of immune cell activation, yet their role in … Read more

J Immunol. 2026 Aug 4;215(8):vkaf313. doi: 10.1093/jimmun/vkaf313. ABSTRACT COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by … Read more

J Immunol. 2026 Aug 4;215(8):vkag225. doi: 10.1093/jimmun/vkag225. ABSTRACT Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease targeting muscle and extramuscular organs, but the molecular mechanisms driving IIM pathogenesis remain largely undefined. Muscle fibroblasts are central to orchestrating inflammation in myositis. Here, we investigated muscle fibroblast dynamics using a single-cell RNA sequencing approach in an … Read more

J Immunol. 2026 Aug 4;215(8):vkag208. doi: 10.1093/jimmun/vkag208. ABSTRACT People with HIV (PWH) exhibit persistent immune activation despite effective antiretroviral therapy, contributing to risk of non-AIDS-associated comorbidities such as cancer. Cell populations reflecting immune remodeling trajectories preceding malignancy are poorly characterized. Using peripheral blood mononuclear cells from an adult cohort (25-65 yr), we quantified the tetraspanin … Read more

J Immunol. 2026 Aug 4;215(8):vkag210. doi: 10.1093/jimmun/vkag210. ABSTRACT Class I MHC peptide (MHC-Ip) multimers are well-established reagents that detect antigen-specific T cells. The classical method for production of MHC-Ip multimers begins with the expression of MHC heavy chains (HCs) and β2-microglobulin (β2m) subunits as inclusion bodies in Escherichia coli and is followed by denaturant solubilization, … Read more

J Immunol. 2026 Jul 10;215(7):vkag186. doi: 10.1093/jimmun/vkag186. ABSTRACT Interleukin (IL)-22 mediates immune cell communication with nonhematopoietic cells and was shown to exert protective or destructive effects in different disease contexts. In the oral mucosal disease periodontitis, IL-22 has been associated with increased tissue destruction, although cause-and-effect evidence and the underlying mechanisms are lacking. Here, we … Read more

J Immunol. 2026 Jul 10;215(7):vkag195. doi: 10.1093/jimmun/vkag195. ABSTRACT Immune platelet transfusion refractoriness (iPTR) is a major complication in transfusion medicine. Although anti-HLA antibodies are recognized contributors, the mechanisms by which they drive platelet clearance remain incompletely defined. We examined sera from 18 patients with iPTR and found that anti-HLA antibodies induced uptake of human platelets … Read more

J Immunol. 2026 Jul 10;215(7):vkag154. doi: 10.1093/jimmun/vkag154. ABSTRACT The postnatal T‑cell pool comprises cells at diverse developmental stages, complicating efforts to resolve T‑cell differentiation, maturation, and long‑term adaptation. To address this challenge, we developed Rag1‑mediated time-stamp tracing, a genetic strategy that enables time‑resolved tracking of T‑cell developmental origins. We validate the specificity and temporal resolution … Read more

J Immunol. 2026 Jul 10;215(7):vkag172. doi: 10.1093/jimmun/vkag172. ABSTRACT The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4+ T cells are affected by … Read more

J Immunol. 2026 Jul 10;215(7):vkag173. doi: 10.1093/jimmun/vkag173. ABSTRACT Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group … Read more

J Immunol. 2026 Jul 10;215(7):vkag205. doi: 10.1093/jimmun/vkag205. ABSTRACT Our laboratory has previously described a mouse model (CD40LΔ5) that produces 60% of wild-type CD40L due to a targeted deletion in an RNA binding site within the CD40L message. The CD40LΔ5 mutation, which destabilizes CD40L mRNA during T-cell activation, causes disrupted germinal center (GC) formation, leading to … Read more

J Immunol. 2026 Jul 10;215(7):vkag202. doi: 10.1093/jimmun/vkag202. ABSTRACT Effector gene expression in CD8+ T cells is tightly controlled at the epigenetic and transcriptional levels; however, crucial regulatory signals remain incompletely understood. In this study, we identify dual specificity phosphatase 2 (DUSP2) as a key epigenetic modulator of effector CD8+ T-cell state, by elucidating inhibition of … Read more

J Immunol. 2026 Jul 10;215(7):vkag204. doi: 10.1093/jimmun/vkag204. ABSTRACT Natural killer (NK) cells are cytotoxic innate lymphoid cells that play a critical role in tumor surveillance by releasing proinflammatory cytokines and cytotoxic granules. NKp44 is an activating receptor that promotes NK cell secretion of TNF and IFN-γ upon engaging platelet-derived growth factor D (PDGF-DD), a ligand … Read more

J Immunol. 2026 Jul 10;215(7):vkag194. doi: 10.1093/jimmun/vkag194. ABSTRACT The TNF‑like cytokine TL1A is a key regulator of immune responses through engagement of its receptor, death receptor 3 (DR3), and has emerged as a therapeutic target in inflammatory diseases. Prevailing models propose that TL1A binding initiates recruitment of adaptor proteins to DR3, leading to downstream signaling. … Read more

J Immunol. 2026 Jul 10;215(7):vkag196. doi: 10.1093/jimmun/vkag196. ABSTRACT Influenza B infection is an important source of morbidity and mortality, especially in vulnerable populations such as children. Improved vaccines and antiviral therapeutics are hindered by gaps in knowledge about influenza B viruses (IBVs). We examined the immune responses in the lung, at the kinetic interface between … Read more

J Immunol. 2026 Jul 10;215(7):vkag211. doi: 10.1093/jimmun/vkag211. ABSTRACT Obesity increases cancer incidence and aggressiveness but is paradoxically associated with improved response to immunotherapy. Here, we show that intratumoral levels of leptin (LEP), a factor contributing to the development of obesity, predict improved outcomes of breast and liver cancers. In contrast, these levels of LEP are … Read more

J Immunol. 2026 Jul 10;215(7):vkag203. doi: 10.1093/jimmun/vkag203. ABSTRACT The innate immune system can detect infection, tissue damage, and other homeostatic disruptions to initiate an immune response, drive inflammation, and promote programmed cell death. While these responses can be beneficial in host defense, aberrant activation of inflammatory, lytic cell death pathways can be pathogenic. Emerging evidence … Read more

J Immunol. 2026 Jul 10;215(7):vkag175. doi: 10.1093/jimmun/vkag175. ABSTRACT The adaptor protein SLP-76 plays a critical role in T-cell receptor signaling and immune activation, yet its relevance in inflammatory bowel disease (IBD) remains unclear. Although calcineurin inhibitors such as cyclosporine A (CsA) are used in severe ulcerative colitis, voclosporin (VCS), a novel calcineurin inhibitor approved for … Read more

J Immunol. 2026 Jul 10;215(7):vkag197. doi: 10.1093/jimmun/vkag197. ABSTRACT Platelets are small, anucleate cells derived from megakaryocytes and are known for their essential role in hemostasis. Over the past decade, they have also emerged as important immune modulators, able to affect viral replication and leukocyte behavior. Most studies on platelets and viral infections have been focused … Read more

J Immunol. 2026 Jul 10;215(7):vkag190. doi: 10.1093/jimmun/vkag190. ABSTRACT Hematopoietic cell transplantation (HCT) is a curative immunotherapy for hematologic malignancies such as acute myeloid leukemia, primarily through graft-versus-tumor (GVT) effects mediated by donor T cells. However, up to 60% of recipients develop graft-versus-host disease (GVHD), with intestinal involvement being a major contributor to morbidity and mortality. … Read more

J Immunol. 2026 Jul 10;215(7):vkag192. doi: 10.1093/jimmun/vkag192. ABSTRACT Human leukocyte antigen class II genes are highly polymorphic. This raises the question of how polymorphisms are distributed across the entirety of the class II molecule and how this distribution affects function. We performed a comprehensive analysis of amino acid variability across the entire class II molecule, … Read more

J Immunol. 2026 Jul 10;215(7):vkag176. doi: 10.1093/jimmun/vkag176. ABSTRACT Colorectal cancer (CRC) is a leading malignancy with limited treatment options at advanced stages. Interleukin (IL)-17 signaling promotes tumor progression and immune evasion. Kaempferol, a natural flavonol, has anti-inflammatory and antitumor effects, but its role in modulating IL-17 pathways in CRC is unclear. We used an immunocompetent … Read more

J Immunol. 2026 Jul 10;215(7):vkag148. doi: 10.1093/jimmun/vkag148. ABSTRACT NK cells are classically defined by their rapid cytotoxicity against tumor cells and infected cells and by early inflammatory cytokine production. However, unconventional roles for NK cells as regulators of immunity and tissue homeostasis have recently been uncovered. Beyond their classical roles, NK cells can orchestrate leukocyte … Read more

J Immunol. 2026 Jul 10;215(7):vkag180. doi: 10.1093/jimmun/vkag180. ABSTRACT Toll-like receptors (TLRs) are key sensors of infection and injury, and are critical inducers of inflammation. TLR-induced activation of the NF-κB and MAPK pathways promotes the secretion of mediators of inflammation such as cytokines and chemokines. Control of cytokine production is critically important, as unnecessary inflammatory responses … Read more

J Immunol. 2026 Jul 10;215(7):vkag188. doi: 10.1093/jimmun/vkag188. ABSTRACT We and others have described homeostatic dysregulation of the CD4+ memory T-cell compartment with age. To gain greater insights into this dysregulation, we performed comprehensive single-cell genomic analysis of endogenous memory CD4+ T cells from young and aged mice. This analysis revealed 16 populations, composed of Th1, … Read more

J Immunol. 2026 Jul 10;215(7):vkag142. doi: 10.1093/jimmun/vkag142. ABSTRACT Radiation is an effective site-specific cytotoxic therapy for cancer cells. In preclinical models, CD8 T cells are essential for optimum tumor control by radiation therapy, yet CD8 T cells are radiosensitive and depleted within the treatment field. Irradiated tumors can be refilled with T cells that were … Read more

J Immunol. 2026 Jul 10;215(7):vkag153. doi: 10.1093/jimmun/vkag153. ABSTRACT The mammalian ovary is the dynamic end-organ of the hypothalamic-pituitary-ovarian axis. In this coordinated system, ovarian cells undergo continuous cycles of apoptosis, proliferation, and differentiation. These changes parallel fluctuations in ovarian hormones such as estradiol; however, the ovarian immune microenvironment during high- and low-estradiol states remains incompletely … Read more

J Immunol. 2026 Jul 10;215(7):vkag181. doi: 10.1093/jimmun/vkag181. ABSTRACT Periodic activation of regulatory T cells (Tregs) is necessary to restrict autoreactive T cells and maintain immune homeostasis. IL-2-STAT5 signaling instructs several metabolic processes underlying Treg activation, including the mevalonate pathway, which is crucial for optimal Treg responses. However, direct links between IL-2-STAT5, mevalonate, and Treg function … Read more

J Immunol. 2026 Jul 10;215(7):vkag031. doi: 10.1093/jimmun/vkag031. ABSTRACT Somatic hypermutation of immunoglobulin (Ig) genes in germinal center B cells is based on the introduction of DNA lesions by activation-induced cytidine deaminase (AID), followed by lesion processing by multiple error-prone DNA repair pathways. Error-free DNA repair by homologous recombination (HR) is required for the repair of … Read more

J Immunol. 2026 Jul 10;215(7):vkag184. doi: 10.1093/jimmun/vkag184. ABSTRACT Acute myeloid leukemia (AML) is a malignant clonal expansion of myeloid progenitor cells that impedes normal hematopoiesis and culminates in bone marrow failure and death. The development of chemoresistant disease in response to first-line chemotherapies is common and indicates a need for new therapies. Tumor-specific mRNA vaccines … Read more

J Immunol. 2026 Jul 10;215(7):vkag185. doi: 10.1093/jimmun/vkag185. ABSTRACT Thymic B cells rely on T cells and type-III IFN (IFN-λ) signaling for class switch recombination and effective licensing as APCs, a process essential for their role in establishing central T-cell tolerance. IFN-λ is produced exclusively by a subset of medullary thymic epithelial cells (mTECs); however, the … Read more

J Immunol. 2026 Jul 10;215(7):vkag193. doi: 10.1093/jimmun/vkag193. ABSTRACT Polymyxins are cyclic cationic lipopeptide antibiotics that disrupt both the outer and inner membranes of Gram-negative bacteria. They also bind to bacterial lipopolysaccharides (LPSs), thereby inhibiting LPS recognition by Toll-like receptor 4 (TLR4) and preventing macrophage activation. However, the immunomodulatory effects of polymyxin B during infection, in … Read more

J Immunol. 2026 Jul 10;215(7):vkag182. doi: 10.1093/jimmun/vkag182. ABSTRACT Endemic coronaviruses circulate seasonally and, while typically mild, can produce robust inflammation and severe pneumonia. Immunological memory to coronaviruses can be cross-reactive for multiple coronaviruses including OC43 and SARS-CoV-2. In this study, we used mouse models to investigate immune responses elicited by pulmonary infection with OC43. OC43 … Read more

J Immunol. 2026 Jul 10;215(7):vkag167. doi: 10.1093/jimmun/vkag167. ABSTRACT γδ T cells are associated with favorable outcomes in many cancers likely through a mechanism of stress-directed cytotoxicity and antitumor cytokine production. Vδ1 γδ T cells are especially promising for immunotherapy due to their broad stress recognition and resistance to activation-induced cell death. Here, we generate a … Read more

J Immunol. 2026 Jul 10;215(7):vkag174. doi: 10.1093/jimmun/vkag174. ABSTRACT Whole-body irradiation (WBI) consistently induces radiation-associated lymphopenia, a complication linked to poor prognosis and reduced overall survival. Understanding the quantitative and qualitative changes in naïve CD4 T cells after WBI is critical because these cells play key roles in both host defense and the propagation of autoimmunity. … Read more

J Immunol. 2026 Jul 10;215(7):vkag104. doi: 10.1093/jimmun/vkag104. NO ABSTRACT PMID:42437361 | DOI:10.1093/jimmun/vkag104

J Immunol. 2026 Jul 10;215(7):vkag171. doi: 10.1093/jimmun/vkag171. ABSTRACT Anti-PD-1 monotherapy has shown a significant survival benefit for patients with advanced-stage melanoma. In this study, we explored whether long-term clinical benefit is determined by abundance or changes in such abundances of CD4 and CD8 T-cell subsets in blood. Peripheral blood mononuclear cells from 58 patients with … Read more

J Immunol. 2026 Jul 10;215(7):vkag163. doi: 10.1093/jimmun/vkag163. ABSTRACT Success of B cell depletion therapy in multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system, places B cells and their functions center stage in efforts to fully understand pathogenesis. Historically, MS animal models of experimental autoimmune encephalomyelitis have featured B cell-independent disease driven … Read more

J Immunol. 2026 Jul 10;215(7):vkag183. doi: 10.1093/jimmun/vkag183. ABSTRACT Chronic viral infections evade or suppress host immunity, posing risks to global human health. However, the underlying mechanisms of viral immune suppression are incompletely defined. Previously, we have demonstrated that sphingosine kinase 2 (SphK2) represses CD4+ T-cell immunity during lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl 13) … Read more

J Immunol. 2026 Jul 10;215(7):vkag162. doi: 10.1093/jimmun/vkag162. ABSTRACT Our group discovered a mutation in a French-Canadian family causing a severe and early-onset form of emphysema. The heterozygote mutation located in the PTPN6 gene causes an alanine to threonine switch near the catalytic site of SHP-1, leading to a reduction of its enzymatic activity. In this … Read more

J Immunol. 2026 Jun 7;215(6):vkag155. doi: 10.1093/jimmun/vkag155. ABSTRACT Staphylococcus aureus (SA), the most common cystic fibrosis (CF) respiratory pathogen, is uniquely capable of producing superantigen (SAg) exotoxins, which are recognized as the most potent activators of the immune system and inducers of inflammation. Although a high frequency of CF SA isolates can produce SA-SAgs, their … Read more

J Immunol. 2026 Jun 7;215(6):vkag140. doi: 10.1093/jimmun/vkag140. ABSTRACT Acute lung injury (ALI) is a fulminant respiratory failure syndrome with no targeted therapy. We show that Inhba is sharply upregulated in the damaged lung tissue of mice and in BEAS-2B cells, and its abundance tracks with cytokine storm and reactive oxygen species (ROS). Mechanistically, AKT activation … Read more

J Immunol. 2026 Jun 7;215(6):vkag164. doi: 10.1093/jimmun/vkag164. ABSTRACT Memory CD8 T cells respond rapidly upon antigen re-encounter and are considered advantageous for protective immunity. However, they undergo a swift decline under chronic antigen stimulation. In this study, we found that memory CD8 T cells’ heightened activation sensitivity promotes terminal differentiation and impairs the formation of … Read more

J Immunol. 2026 Jun 7;215(6):vkag177. doi: 10.1093/jimmun/vkag177. ABSTRACT In humans, infection with Chlamydia trachomatis can result in chronic infection with severe reproductive consequences. The immune response elicited by natural infection fails to protect against reinfection and can contribute to tissue inflammation and damage. CD4+ T cells are key mediators of protection against C. trachomatis. However, … Read more

J Immunol. 2026 Jun 7;215(6):vkag145. doi: 10.1093/jimmun/vkag145. ABSTRACT Regulatory T cells (Tregs) are critical guardians of immune homeostasis that must operate in diverse and often inflammatory conditions. However, the mechanisms that Tregs use to maintain their stability and function, especially in response to the stresses of distinct microenvironments, remain incompletely understood. Previous work identified the … Read more

J Immunol. 2026 Jun 7;215(6):vkag115. doi: 10.1093/jimmun/vkag115. ABSTRACT Inhalation of house dust mite-derived allergens is a major factor leading to the development of asthma both in children and adults. Allergens stimulate Ca2+-dependent pro-inflammatory cytokine and chemokine gene expression through the opening of ORAI1 Ca2+ channels in the surface membrane of various immune cell-types within the … Read more

J Immunol. 2026 Jun 7;215(6):vkag161. doi: 10.1093/jimmun/vkag161. ABSTRACT Neurotrophic keratitis (NK) arises when trigeminal sensory dysfunction reduces corneal sensation and compromises epithelial maintenance. Herpes simplex virus type 1 (HSV-1) establishes latency in the trigeminal ganglion (TG) and is a common trigger of acquired NK, yet the host programs that determine whether inflamed ganglia recover or … Read more

J Immunol. 2026 Jun 7;215(6):vkag131. doi: 10.1093/jimmun/vkag131. ABSTRACT Type I interferons (IFNs) are central antiviral cytokines in vertebrates, yet the mechanisms underlying their functional diversification in early vertebrates remain unclear. Teleost fish, whose IFN repertoires expanded through whole-genome duplication, provide a powerful model to address this question. Here, we systematically characterize grass carp (Ctenopharyngodon idella) … Read more

J Immunol. 2026 Jun 7;215(6):vkag136. doi: 10.1093/jimmun/vkag136. ABSTRACT Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, how differences in affinity and specificity may support Treg function compared with autoimmune T cell function remains unresolved. In this study, we analyzed the T cell receptor (TCR) repertoires of the regulatory and effector T … Read more

J Immunol. 2026 Jun 7;215(6):vkag132. doi: 10.1093/jimmun/vkag132. ABSTRACT The finTRIM (FTR) subfamily, a group of fish-specific tripartite motif proteins, has arisen through gene duplication events specific to particular genera or species. However, the regulatory mechanisms of FTR in antiviral immune response remains largely unknown. In the present study, we identified a fish novel tripartite motif … Read more

J Immunol. 2026 Jun 7;215(6):vkag094. doi: 10.1093/jimmun/vkag094. ABSTRACT MR1 is a non-polymorphic, ubiquitously expressed, MHC class I-like antigen-presenting molecule that presents small-molecule metabolites to T cells. Studies have shown that MR1 plays a role in microbial infection, inflammation, and tumor immunity. The antigens it presents include metabolites of microbial and self-origin as well as small-molecule … Read more

J Immunol. 2026 Jun 7;215(6):vkag134. doi: 10.1093/jimmun/vkag134. ABSTRACT Gamma delta (γδ) T cells undergo a distinct developmental pathway within the thymus, where transforming growth factor β (TGF-β) exerts pivotal regulatory influence. However, the precise mechanistic contributions of TGF-β to γδ T cells differentiation and functional maturation remain incompletely understood. Here, we show that TGF-β regulates … Read more

J Immunol. 2026 Jun 7;215(6):vkag157. doi: 10.1093/jimmun/vkag157. ABSTRACT The complement system and natural killer (NK) cells play crucial roles in tumor growth and metastasis. The role of the complement system in affecting the phenotype and anti-tumor function of NK cells remains poorly understood. Using the B16F10 mouse melanoma model, we demonstrated that NK cells from … Read more

J Immunol. 2026 Jun 7;215(6):vkag169. doi: 10.1093/jimmun/vkag169. ABSTRACT Interferons (IFNs) affect almost all nucleated cells and induce transcriptional events that are associated with control of intracellular infections as well as regulatory pathways that influence inflammatory processes. How different hematopoietic and non-hematopoietic cell types interpret these signals is a reflection of cellular context and function. For … Read more

J Immunol. 2026 Jun 7;215(6):vkag165. doi: 10.1093/jimmun/vkag165. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) in which cancer-associated fibroblasts (CAFs) play pivotal roles in shaping therapeutic responses. Among these, MHC-II-expressing antigen-presenting CAFs (apCAFs) modulate CD4 T-cell activity, yet their contribution to the antitumor immune response remains unclear. Using tumor clones … Read more

J Immunol. 2026 Jun 7;215(6):vkag158. doi: 10.1093/jimmun/vkag158. ABSTRACT In human melanoma, tumor cell-specific MHC class II expression is associated with improved response to programmed death 1 and programmed death-ligand 1 blockade; yet the direct effect of melanoma cell-specific MHC class II expression on anti-melanoma T cell responses remains largely unknown. In the clinically relevant Yale … Read more

J Immunol. 2026 Jun 7;215(6):vkag127. doi: 10.1093/jimmun/vkag127. ABSTRACT Downregulation of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been implicated in autophagic cell death. However, how ENPP1 regulates the interplay between autophagy and ferroptosis to maintain trophoblast homeostasis in the context of gestational diabetes mellitus (GDM) remains unclear. To determine ENPP1’s role in autophagy-dependent ferroptosis and its contribution … Read more

J Immunol. 2026 Jun 7;215(6):vkag151. doi: 10.1093/jimmun/vkag151. ABSTRACT Inflammatory diseases arise from complex interactions between immune signaling and cellular stress. Although endoplasmic reticulum (ER) stress is a key modulator of immunity, the mechanisms by which it promotes inflammatory pathology remain incompletely understood. Notably, ER stress-induced NF-κB activation alone is insufficient to account for robust IL-6 … Read more

J Immunol. 2026 Jun 7;215(6):vkag160. doi: 10.1093/jimmun/vkag160. ABSTRACT The V158F polymorphism found in the human Fc receptor CD16a (also known as FcγRIIIa) is thought to influence autoimmune disorders and responses to IgG-based therapies. V158F is known to influence the IgG affinity, and thereby triggering of the CD16a receptor expressed on various immune cells. In contrast … Read more

J Immunol. 2026 Jun 7;215(6):vkag168. doi: 10.1093/jimmun/vkag168. ABSTRACT Forkhead Box P1 (Foxp1) is a transcription factor critical for the proper development of multiple tissues. While Foxp1 has a well-described role in regulating adaptive immunity through modulation of T and B cells, a function in medullary thymic epithelial cells (mTECs) has not been reported. Here we … Read more

J Immunol. 2026 Jun 7;215(6):vkag170. doi: 10.1093/jimmun/vkag170. ABSTRACT Memory T-cell inflation is a distinctive immunological phenomenon observed during persistent viral infections such as cytomegalovirus (CMV). Unlike conventional memory T-cell responses, which contract after infection resolution, a subset of CMV-specific T cells undergoes a progressive and sustained expansion, termed “inflation”, which is thought to be critical … Read more