Journal of Immunology

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

J Immunol. 2026 Jun 7;215(6):vkag135. doi: 10.1093/jimmun/vkag135. ABSTRACT Regulators of G protein signaling (RGS) deactivate G proteins associated with G protein-coupled receptors (GPCRs), a large receptor family with diverse functions. Of the 20 RGS, the Rgs14 single-nucleotide polymorphism is associated with inflammatory bowel disease, and Rgs14 expression is higher in macrophages than in epithelial cells. … Read more

J Immunol. 2026 Jun 7;215(6):vkag143. doi: 10.1093/jimmun/vkag143. ABSTRACT Acquired immunity in mammals depends upon capture and presentation of antigens by specialized macrophage populations in splenic marginal zone and lymph node sinuses and follicular dendritic cells within germinal centers. Cells referred to as follicular dendritic cells in chickens express CSF1R, the receptor for CSF1 and IL34. … Read more

J Immunol. 2026 Jun 7;215(6):vkag133. doi: 10.1093/jimmun/vkag133. ABSTRACT Reproducible and efficient genetic engineering of human NK cells remains a primary challenge to next-generation chimeric antigen receptor (CAR) therapies, specifically for larger constructs with multiple plasmids and transgenes. Lentiviral vectors (LVs) pseudotyped with baboon envelope (BaEV) outperform vesicular stomatitis virus G protein in transducing hematopoietic stem … Read more

J Immunol. 2026 Jun 7;215(6):vkag137. doi: 10.1093/jimmun/vkag137. ABSTRACT In the canonical model of VDJ recombination, a single diversity (D) gene is incorporated into the complementarity-determining region 3 (CDR3) to produce a T cell receptor δ (TCRδ; TRD) or TCRβ (TRB) chain. But by constructing a dataset of more than 2.7 million TRD CDR3 sequences from … Read more

J Immunol. 2026 Jun 7;215(6):vkag125. doi: 10.1093/jimmun/vkag125. ABSTRACT Severe trauma triggers a dynamic disturbance of immune function that can progress from early hyperinflammation to prolonged dysregulation, increasing patient vulnerability to infection and chronic critical illness (CCI). To identify immune features linked to different postinjury clinical trajectories, we prospectively evaluated severely injured trauma patients and categorized … Read more

J Immunol. 2026 Jun 7;215(6):vkag139. doi: 10.1093/jimmun/vkag139. ABSTRACT Protective immunity is induced by both, wild-type measles virus (WT MeV) and live-attenuated (LA) measles virus vaccine (LAMV), affording the opportunity to compare common and selective immunological underpinnings of immune protection. Here, peripheral blood mononuclear cells (PBMCs) were collected from rhesus macaques at several timepoints after infection … Read more

J Immunol. 2026 Jun 7;215(6):vkag159. doi: 10.1093/jimmun/vkag159. ABSTRACT The major capsid protein (MCP), owing to its strong immunogenicity, has emerged as a critical target for largemouth bass ranavirus (LMBV) vaccine development. However, its key antigenic epitopes remain uncharacterized. This study integrated phage display technology with bioinformatics approaches to design a multiepitope vaccine against LMBV. By … Read more

J Immunol. 2026 Jun 7;215(6):vkag149. doi: 10.1093/jimmun/vkag149. ABSTRACT Pathogen-derived RNAs function as pathogen-associated molecular patterns (PAMPs) that activate innate immune responses through pattern recognition receptors (PRRs). While viral RNA is well established as a trigger of antiviral immunity, the identity of bacterial RNA species that function as immunostimulatory ligands and the host PRRs that recognize … Read more

J Immunol. 2026 Jun 7;215(6):vkag114. doi: 10.1093/jimmun/vkag114. ABSTRACT Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is associated with clinical diversity and outcomes ranging from latent TB to active TB with distinct pathophysiologies. However, our understanding of the innate immune mechanisms related to the protection or progression of TB is limited. Among innate immune cells, the … Read more

J Immunol. 2026 Jun 7;215(6):vkag126. doi: 10.1093/jimmun/vkag126. ABSTRACT Germinal centers (GCs) are microanatomical structures in which antigen-specific B cells undergo proliferation, somatic hypermutation, and affinity-based competition to select high-affinity clones that differentiate into memory B cells and plasma cells (PCs). B cell progression through the GC is tightly regulated, and the molecular determinants that modulate … Read more

J Immunol. 2026 Jun 7;215(6):vkag147. doi: 10.1093/jimmun/vkag147. ABSTRACT Cell-to-cell communication is essential for maintaining homeostasis and coordinating complex biological processes in multicellular organisms. Classically, cells communicate using secreted peptides and metabolites and through cell contact-dependent signaling. Emerging studies over the past 20 years indicate that many cell types, including innate immune cells such as macrophages, … Read more

J Immunol. 2026 Jun 7;215(6):vkag118. doi: 10.1093/jimmun/vkag118. ABSTRACT Glycoprotein 130 (GP130) is an archetypal class I cytokine receptor that serves as a shared signalling subunit for a group of cytokines known as interleukin 6 (IL-6)-type cytokines. GP130 does not have an intrinsic kinase activity and relies on Janus kinases (JAK) 1, 2, or Tyrosine kinase … Read more

J Immunol. 2026 Jun 7;215(6):vkaf345. doi: 10.1093/jimmun/vkaf345. NO ABSTRACT PMID:42311113 | DOI:10.1093/jimmun/vkaf345

J Immunol. 2026 Jun 7;215(6):vkag144. doi: 10.1093/jimmun/vkag144. ABSTRACT Neuroblastoma (NB) is the most common extracranial solid tumor in children and remains a major therapeutic challenge in high-risk patients because of frequent recurrence and metastasis. γδT cells are a unique lymphocyte subset with potent antitumor activity and are widely distributed in NB tumors. However, the immunosuppressive … Read more

J Immunol. 2026 Jun 7;215(6):vkag120. doi: 10.1093/jimmun/vkag120. ABSTRACT Checkpoint inhibitors have transformed cancer treatment, yet predicting responses remains challenging. Mitochondrial quality decreases in tumor infiltrating lymphocytes and correlates with impaired antitumor immunity in animal models. Mitochondrial membrane potential (MMP) increases with T cell activation and may also indicate cellular dysfunction. Here, we assessed the MMP … Read more

J Immunol. 2026 Jun 7;215(6):vkag129. doi: 10.1093/jimmun/vkag129. ABSTRACT Despite an effective vaccine against the hepatitis B virus (HBV), there are about 250 million people living with chronic HBV (CHB) worldwide and one million deaths annually. Most children and about 5% of adults exposed to HBV will fail to clear the virus, developing a lifelong infection. … Read more

J Immunol. 2026 Jun 7;215(6):vkag095. doi: 10.1093/jimmun/vkag095. NO ABSTRACT PMID:42309535 | DOI:10.1093/jimmun/vkag095

J Immunol. 2026 Jun 7;215(6):vkag055. doi: 10.1093/jimmun/vkag055. NO ABSTRACT PMID:42309534 | DOI:10.1093/jimmun/vkag055

J Immunol. 2026 Jun 7;215(6):vkag146. doi: 10.1093/jimmun/vkag146. ABSTRACT In inflammatory tissue niches, macrophages encounter intense oxidative stress due to their own production of reactive oxygen and nitrogen species as part of antimicrobial defense. Our findings reveal that inflammatory macrophages deploy distinct, context-dependent redox-protective mechanisms to survive this self-inflicted stress, thereby avoiding ferroptotic cell death. Specifically, … Read more

J Immunol. 2026 Jun 7;215(6):vkag156. doi: 10.1093/jimmun/vkag156. NO ABSTRACT PMID:42300803 | DOI:10.1093/jimmun/vkag156

J Immunol. 2026 Jun 7;215(6):vkag116. doi: 10.1093/jimmun/vkag116. ABSTRACT Interferon-gamma (IFN-γ) is a powerful transactivating signal eliciting hundreds of IFN-stimulated genes (ISGs) in humans to help combat infection. Most ISGs remain uncharacterized, and here we searched for actin-binding candidates that could potentially target intracellular pathogens to block their spread or promote immune cell migration into infected … Read more

J Immunol. 2026 Jun 7;215(6):vkaf379. doi: 10.1093/jimmun/vkaf379. NO ABSTRACT PMID:42295821 | DOI:10.1093/jimmun/vkaf379

J Immunol. 2026 Jun 7;215(6):vkag099. doi: 10.1093/jimmun/vkag099. ABSTRACT Gamma delta (γδ) T cells emerge early during human gestation and are uniquely equipped to protect the fetus and infant following infection, due to their innate-like recognition of conserved molecular ligands. Following congenital cytomegalovirus infection (cCMV), Vδ1 T cells have been shown to expand, differentiate, and upregulate … Read more

J Immunol. 2026 Jun 7;215(6):vkaf377. doi: 10.1093/jimmun/vkaf377. NO ABSTRACT PMID:42295822 | DOI:10.1093/jimmun/vkaf377

J Immunol. 2026 Jun 7;215(6):vkag109. doi: 10.1093/jimmun/vkag109. ABSTRACT Defective resolution of inflammation following sepsis contributes to persistent immune dysfunction and increased morbidity and mortality worldwide. Efficient clearance of apoptotic polymorphonuclear neutrophils (PMNs) by macrophages, a process known as efferocytosis, is essential for resolving inflammation, promoting tissue repair, and restoring immune homeostasis; however, the molecular mechanisms … Read more

J Immunol. 2026 Jun 7;215(6):vkag138. doi: 10.1093/jimmun/vkag138. ABSTRACT Salmonella enterica is a gastrointestinal pathogen that causes a variety of intestinal and systemic clinical disease. Vaccine development for systemic salmonellosis requires a deeper understanding of protective mechanisms and the relative contribution of mucosal and systemic host responses to bacterial elimination. Here, we examined the relative importance … Read more

J Immunol. 2026 Jun 7;215(6):vkag128. doi: 10.1093/jimmun/vkag128. ABSTRACT Despite a vast literature on the role of macrophages in wound healing, the role of dermal monocyte (Mo)-derived antigen presenting cells (APC) has received scant attention. Using scRNAseq and flow cytometry, we identify a population of APC that is prominent in wounds of non-diabetic mice but is … Read more

J Immunol. 2026 Jun 7;215(6):vkag105. doi: 10.1093/jimmun/vkag105. ABSTRACT Modulation of T cell receptor (TCR) sensitivity during positive selection is critical to avoid negative selection and direct thymocytes into their appropriate lineage. Thymocytes just prior to positive selection (preselection) are highly responsive to low affinity self-ligands and are also actively rearranging their TCRα locus as they … Read more

J Immunol. 2026 Jun 7;215(6):vkag113. doi: 10.1093/jimmun/vkag113. ABSTRACT N-linked glycosylation (N-glyc) sites (N-X-S/T, X≠P) can be introduced by somatic hypermutation in immunoglobulin Fab regions. In patients with rheumatoid arthritis (RA), anti-citrullinated protein antibodies have a striking overrepresentation of Fab N-glycosylation. To further explore this, we sequenced B cell receptors (BCRs) from peripheral blood of 13 … Read more

J Immunol. 2026 Jun 7;215(6):vkag101. doi: 10.1093/jimmun/vkag101. ABSTRACT Efficient tissue regeneration requires the precise coordination of inflammatory and regenerative programs, principally mediated by monocyte-derived macrophages. However, the transcriptional wiring and epigenomic processes behind complex macrophage subtype specification and transition between the different states are not known. Here we have identified the transcriptional repressor BACH1 as … Read more

J Immunol. 2026 Jun 7;215(6):vkag110. doi: 10.1093/jimmun/vkag110. ABSTRACT The cytokines interleukin (IL)-22 and IL-17 are secreted by innate and adaptive immune cells to drive “type III” responses that protect against extracellular pathogens, promote mucosal barrier integrity, and foster microbiota homeostasis. However, dysregulation of IL-22 and/or IL-17 contributes to autoimmunity, chronic inflammation, and malignancy. Thus, a … Read more

J Immunol. 2026 Jun 7;215(6):vkag091. doi: 10.1093/jimmun/vkag091. ABSTRACT Viral or tumor persistence is often associated with CD8 T cell “exhaustion,” a differentiation process characterized by co-inhibitory receptor upregulation and loss of effector function. Recent data show that “exhausted” T cells are a heterogenous population that includes a progenitor subset that transitions through an intermediate state … Read more

J Immunol. 2026 Jun 7;215(6):vkag074. doi: 10.1093/jimmun/vkag074. ABSTRACT Messenger RNA (mRNA) vaccines effectively induce protective immunity, but antigen-specific CD8+ T cell responses exhibit limited persistence. In this study, we aimed to assess CD8+ T cell responses following a third dose of the Pfizer BNT162b2 COVID-19 vaccine and identify factors contributing to their longevity. Using HLA … Read more

J Immunol. 2026 Jun 7;215(6):vkag130. doi: 10.1093/jimmun/vkag130. ABSTRACT Sepsis is the leading cause of death in hospitals and is very common in intensive care units (ICUs). Sleep is frequently interrupted in the hospital setting, especially within the ICU. Patients who sleep poorly have worse outcomes, such as increased mortality and longer hospital stays; however, the … Read more

J Immunol. 2026 Jun 7;215(6):vkag124. doi: 10.1093/jimmun/vkag124. ABSTRACT Group 2 innate lymphoid cells (ILC2s) are thought to develop in the bone marrow and fetal liver. However, increasing evidence supports the presence of thymic ILC2s in mice and humans. In this study, we introduce a novel fate-mapping mouse model designed to track thymic ILC2s in peripheral … Read more

J Immunol. 2026 Jun 7;215(6):vkag117. doi: 10.1093/jimmun/vkag117. ABSTRACT Mucosal immunity is paramount for combating respiratory infections, but conventional vaccination methods, such as intramuscular injection, often struggle to induce it. Although direct mucosal vaccination is effective, it carries an increased risk of respiratory adverse effects, making it particularly challenging for individuals with chronic respiratory diseases. Consequently, … Read more

J Immunol. 2026 Jun 7;215(6):vkag122. doi: 10.1093/jimmun/vkag122. ABSTRACT Interferon-induced transmembrane (IFITM) proteins underpin antiviral responses, yet their role in bacterial infections remains underexplored, particularly for parasites. We probed the role of IFITM1 in Mycobacterium tuberculosis (Mtb), Listeria monocytogenes (Lm), and Leishmania major infection using IFITM1 knockout mice. Notably, IFITM1 was upregulated in murine and human … Read more

J Immunol. 2026 May 14;215(5):vkag069. doi: 10.1093/jimmun/vkag069. ABSTRACT Burkholderia thailandensis (B. thailandensis) is an emerging pathogen. Although it has not yet caused large-scale outbreaks, severe infections can lead to sepsis. Currently, there are no effective treatment strategies available, highlighting the urgent need to develop novel therapies. Progranulin (PGRN) is a multifunctional protein with complex roles … Read more

J Immunol. 2026 May 14;215(5):vkag047. doi: 10.1093/jimmun/vkag047. NO ABSTRACT PMID:42229912 | DOI:10.1093/jimmun/vkag047

J Immunol. 2026 May 14;215(5):vkaf166. doi: 10.1093/jimmun/vkaf166. NO ABSTRACT PMID:42226503 | DOI:10.1093/jimmun/vkaf166

J Immunol. 2026 May 14;215(5):vkag108. doi: 10.1093/jimmun/vkag108. ABSTRACT T cell exhaustion remains a significant barrier to effective adoptive cell therapy in solid tumors. Here, we demonstrate that in vitro treatment with the PI3Kδ inhibitor CAL-101 generates T cells with enhanced stemness and metabolic fitness. These cells show increased mitochondrial dependence and spare respiratory capacity while … Read more

J Immunol. 2026 May 14;215(5):vkag083. doi: 10.1093/jimmun/vkag083. ABSTRACT Rheumatoid arthritis (RA) is characterized by severe synovial inflammation and progressive joint destruction. This study evaluated the therapeutic effects of electroacupuncture (EA) in a rat model of RA and explored its potential association with lipoic acid (LA) metabolism. Collagen-induced arthritis (CIA) was established in rats, followed by … Read more

J Immunol. 2026 May 14;215(5):vkag123. doi: 10.1093/jimmun/vkag123. ABSTRACT Endometriosis is an inflammatory gynecologic disease characterized by ectopic growth of endometrial-like tissue, resulting in pelvic pain and infertility. T-helper 9 (Th9) cells play a known role in various chronic inflammatory diseases. Despite parallels between endometriosis and Th9-driven diseases, their role in endometriosis has not been extensively … Read more

J Immunol. 2026 May 14;215(5):vkag119. doi: 10.1093/jimmun/vkag119. ABSTRACT Regulatory T cells (Tregs) play a crucial role in mediating recovery from acute lung injury (ALI). However, the complex roles of functionally heterogeneous Treg subsets in the lung during the resolution of acute inflammation remain unclear. To investigate the role of peripherally induced Tregs, we utilized mice … Read more