Journal of Immunology

J Immunol. 2026 Oct 1;215(10):vkag272. doi: 10.1093/jimmun/vkag272. ABSTRACT Major histocompatibility complex class Ia (MHC-Ia)-restricted CD8⁺ T cell responses play a central role in the host defense against HIV-1, with certain MHC-Ia alleles known to be associated with cytotoxic T lymphocyte responses having an increased potential for viral control. However, the impact of immune aging on … Read more

J Immunol. 2026 Oct 1;215(10):vkag257. doi: 10.1093/jimmun/vkag257. ABSTRACT Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in human nucleotide-binding domain, leucine-rich repeat-containing protein 3 (NLRP3), which lead to constitutive inflammasome activation and excessive IL-1β secretion. Long-term IL-1 blockade has markedly improved patient outcomes by preventing systemic inflammation and amyloidosis. However, whether … Read more

J Immunol. 2026 Oct 1;215(10):vkag269. doi: 10.1093/jimmun/vkag269. ABSTRACT CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication after transmission and prevent spread to the lower respiratory tract (LRT), whereas LRT CD8+ TRM are important for limiting immunopathology in the lung and promoting efficient viral clearance. Although the presence of … Read more

J Immunol. 2026 Oct 1;215(10):vkag276. doi: 10.1093/jimmun/vkag276. ABSTRACT CTLA-4 is an inhibitory receptor on T cells that limits immune activation by competing with the co-stimulatory receptor CD28 for binding to CD80 and CD86 on antigen-presenting cells. Regulatory T cells (Tregs) employ CTLA-4-mediated transendocytosis as a key suppressive mechanism. Several CTLA4 polymorphisms are associated with autoimmune … Read more

J Immunol. 2026 Oct 1;215(10):vkag270. doi: 10.1093/jimmun/vkag270. ABSTRACT HLA-A*02:01-restricted PB1413+CD8+ T cells provide the broadest reported cross-reactive immunity against influenza A, B, and C viruses. Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2/PB1413+CD8+ T cell pools, compared with immunodominant influenza A-specific M158+CD8+ T cells and codominant influenza B-specific A2/HA543+CD8+ memory … Read more

J Immunol. 2026 Oct 1;215(10):vkag268. doi: 10.1093/jimmun/vkag268. ABSTRACT Multiple sclerosis (MS) is thought to be mediated by human leukocyte antigen (HLA) class II-restricted autoreactive CD4 T cells producing interleukin (IL)-17A and/or interferon γ (IFNγ), but the necessity of these cytokines for disease pathogenesis is unclear. Utilizing HLA-DR3 (DRβ1*0301) transgenic mice lacking IFNγ or IL-17A in … Read more

J Immunol. 2026 Oct 1;215(10):vkag267. doi: 10.1093/jimmun/vkag267. ABSTRACT Manganese ions (Mn2+) are potent immunomodulatory agents that activate the cGAS-STING pathway. While their role as acute adjuvants is well-documented, the innate immune memory (trained immunity) signatures induced by Mn2+ remain unexplored. Using an in vitro priming-rest-challenge model, we demonstrate that transient Mn2+ stimulation induces a persistent … Read more

J Immunol. 2026 Oct 1;215(10):vkag250. doi: 10.1093/jimmun/vkag250. ABSTRACT B cell precursor acute lymphoblastic leukemia (BCP ALL) is driven by a combination of genetic alterations that promote invasion and expansion of undifferentiated B cells. Mice that express a NUP98::HOXD13 (NHD13) fusion gene in hematopoietic cells develop a wide range of hematologic malignancy, and when crossed to … Read more

J Immunol. 2026 Oct 1;215(10):vkag187. doi: 10.1093/jimmun/vkag187. ABSTRACT CD8+ T cells directly target and kill cancer cells and are required for effective antitumor immunity. However, CD8+ T cells may become dysfunctional when exposed to chronic antigen stimulation during cancer. Dysfunction is characterized by reduced proliferation, increased expression of inhibitory receptors, and impaired effector function, yet … Read more

J Immunol. 2026 Oct 1;215(10):vkag258. doi: 10.1093/jimmun/vkag258. ABSTRACT Determining how chemotherapeutic drugs alter the MHC class I-associated immunopeptidome is essential for designing rational combinatorial therapies to enhance antitumor CD8+ T-cell activity, such as immune checkpoint inhibitor Abs. We investigated the impact of a first-in-class inhibitor of cellular NEDDylation, MLN4924, on self-peptide presentation using 2 human … Read more

J Immunol. 2026 Oct 1;215(10):vkag266. doi: 10.1093/jimmun/vkag266. ABSTRACT This study assessed the role that natural killer (NK) cells play in a murine model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike mRNA vaccination. Flow cytometric analyses revealed that mRNA vaccination results in recruitment and maturation of NK cells in the spleen. Primed (CD27+ CD11b+) … Read more

J Immunol. 2026 Oct 1;215(10):vkag249. doi: 10.1093/jimmun/vkag249. ABSTRACT Myeloid-derived suppressor cells are a pivotal component of the immunosuppressive tumor microenvironment in hematologic malignancies. Through diverse mechanisms, they promote disease progression, therapeutic resistance, and immune evasion. This comprehensive review synthesizes current evidence on the roles of myeloid-derived suppressor cells across major hematologic cancers and evaluates their … Read more

J Immunol. 2026 Oct 1;215(10):vkag234. doi: 10.1093/jimmun/vkag234. ABSTRACT Immune checkpoint inhibitor (ICPI) therapy, targeting Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2, have revolutionized cancer care. However, ICPI is linked to immune-related adverse events, including nephropathy manifesting as acute kidney injury (AKI), a rapid decline in kidney function, often progressing to … Read more

J Immunol. 2026 Oct 1;215(10):vkag255. doi: 10.1093/jimmun/vkag255. ABSTRACT Macrophages function as professional antigen-presenting cells that integrate inflammatory signals with metabolic reprogramming to shape immune responses. Itaconate, an immunometabolite derived from ACOD1/IRG1 activity in activated macrophages, has been implicated in the regulation of inflammatory responses, yet its role in interferon γ (IFN-γ)-driven antigen presentation programs remains … Read more

J Immunol. 2026 Oct 1;215(10):vkag264. doi: 10.1093/jimmun/vkag264. ABSTRACT T follicular helper (Tfh) cells provide help to B cells for antibody class switching and affinity maturation and are critical for germinal center (GC) formation. The frequency of Tfh cells has proven to be a valuable marker for predicting durable neutralizing antibody responses; conversely, the expansion of … Read more

J Immunol. 2026 Oct 1;215(10):vkag261. doi: 10.1093/jimmun/vkag261. ABSTRACT Cytotoxic CD8⁺ T lymphocytes eliminate pathogen-infected and malignant cells through migration to affected tissues, cytokine production, and cytotoxic activity. A mounting body of evidence indicates that CD8 T cell differentiation into functionally different subsets, such as effector, memory, tissue-resident memory, and exhausted T cells, is controlled by … Read more

J Immunol. 2026 Oct 1;215(10):vkag265. doi: 10.1093/jimmun/vkag265. ABSTRACT Chlamydia trachomatis is the leading bacterial sexually transmitted pathogen worldwide and a major cause of reproductive tract disease, highlighting the need for an effective vaccine. Defining the immune mechanisms underlying vaccine-induced protection is therefore critical. We previously demonstrated that in mice vaccinated with CTH522/CAF01, genital tract Th17 … Read more

J Immunol. 2026 Aug 29;215(9):vkag232. doi: 10.1093/jimmun/vkag232. ABSTRACT Vaccines comprising peptide antigens for inducing T cell immunity are being developed for a broad range of therapeutic applications including prevention and treatment of cancer, autoimmunity, and infectious diseases. However, many peptide antigens contain cysteine and/or methionine, which are prone to form oxidation products that can present … Read more

J Immunol. 2026 Aug 29;215(9):vkag253. doi: 10.1093/jimmun/vkag253. ABSTRACT The histone-like protein Hup is a highly conserved DNA-stabilizing and compacting protein found across bacterial families. We previously demonstrated that the Hup protein of Staphylococcus and Streptococcus species harbors a shared CD4+ T cell epitope, and that Hup77-88-specific CD4+ T cells confer cross-species protection against pulmonary infection … Read more

J Immunol. 2026 Aug 29;215(9):vkag260. doi: 10.1093/jimmun/vkag260. ABSTRACT T helper 17 (Th17) cell differentiation is governed by a complex transcriptional network centered on the lineage-specifying factor RORγt, accompanied by STAT3, IRF4, and SMAD2/3. However, the complete repertoire of transcriptional regulators controlling Il17a gene transcription and Th17 commitment remains incompletely defined. Here, we identify zinc finger … Read more

J Immunol. 2026 Aug 29;215(9):vkag240. doi: 10.1093/jimmun/vkag240. ABSTRACT This study aimed to investigate the mechanism by which the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin improves immune imbalance in sepsis with diabetes, focusing on its regulation of macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis. A mouse model of type 2 diabetes was established through intraperitoneal injection of … Read more

J Immunol. 2026 Aug 29;215(9):vkag252. doi: 10.1093/jimmun/vkag252. ABSTRACT Current glycoconjugate vaccines often fail to induce durable B cell memory or to provide sufficiently high-affinity antibodies limiting their utility for prophylactic protection against most bacterial and fungal pathogens. We address this limitation by engineering a chemically functionalized protein nanoparticle vaccine capable of eliciting protective nanomolar affinity … Read more

J Immunol. 2026 Aug 29;215(9):vkag259. doi: 10.1093/jimmun/vkag259. ABSTRACT Humans produce 12 distinct interferon alpha (IFN-α) subtypes that were previously thought to be functionally redundant. Recent studies have revealed that IFN-α subtypes differ in their ability to control different viral infections. However, little is known about how IFN-α subtypes differentially modulate immune cells to mediate these … Read more

J Immunol. 2026 Aug 29;215(9):vkag251. doi: 10.1093/jimmun/vkag251. ABSTRACT Inflammatory responses require precise posttranscriptional control of gene expression, yet the contribution of circular RNAs (circRNAs) to this process remains poorly understood. Here, we performed circRNA sequencing in murine macrophages stimulated with lipopolysaccharide (LPS) and identified dynamic and stimulus-dependent changes in circRNA expression. Among 1,298 high-confidence circRNAs, … Read more

J Immunol. 2026 Aug 29;215(9):vkag256. doi: 10.1093/jimmun/vkag256. ABSTRACT The expression, localization, and secretion of certain chromatin proteins are tightly regulated in response to inflammatory challenges or tissue damage. High mobility group (HMG) nucleosome-binding proteins can translocate out of the nucleus to act as alarmins in immune cell communications. The consequences of nuclear depletion of HMGs … Read more

J Immunol. 2026 Aug 29;215(9):vkag254. doi: 10.1093/jimmun/vkag254. ABSTRACT Obesity is a risk factor for severe respiratory viral infections, but its impact on bacterial respiratory diseases remains unclear and is sometimes paradoxical. Herein, we demonstrate that diet-induced obese, male C57BL/6J mice exhibited increased resistance to pulmonary infection with Francisella tularensis and Bordetella pertussis compared with lean … Read more

J Immunol. 2026 Aug 29;215(9):vkag239. doi: 10.1093/jimmun/vkag239. NO ABSTRACT PMID:42763889 | DOI:10.1093/jimmun/vkag239

J Immunol. 2026 Aug 29;215(9):vkag242. doi: 10.1093/jimmun/vkag242. ABSTRACT Laboratory-raised specific pathogen-free (SPF) mice have been indispensable for fundamental immunology research, yet their reliability in predicting human clinical outcomes has been questionable. A major factor contributing to this disconnect is the sanitized housing environment, which deprives laboratory mice of physiological microbial exposure critical for immune maturation. … Read more

J Immunol. 2026 Aug 29;215(9):vkag248. doi: 10.1093/jimmun/vkag248. ABSTRACT Clonal hematopoiesis of indeterminate potential (CHIP) arises from age-related somatic mutations in hematopoietic stem cells in the bone marrow (BM), driving clonal expansion and altered phenotypes. Loss-of-function mutations in the epigenetic regulator TET2 are among the most frequent in CHIP and increase the risk of hematologic malignancies … Read more

J Immunol. 2026 Aug 29;215(9):vkag243. doi: 10.1093/jimmun/vkag243. ABSTRACT Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds … Read more

J Immunol. 2026 Aug 29;215(9):vkag246. doi: 10.1093/jimmun/vkag246. ABSTRACT The dynamic interplay between pro- and anti-inflammatory cytokines plays a crucial role in regulating host immune responses. In our earlier study, we showed that Leishmania donovani-induced IL-33 destabilizes host cytokine dynamics by downregulating TNF-α and IL-12 and ensures intramacrophage parasite survival. Another pertinent host favorable proinflammatory cytokine … Read more

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