Journal of Immunology

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

J Immunol. 2026 May 14;215(5):vkag121. doi: 10.1093/jimmun/vkag121. ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viral pathogens for the swine industry. PRRSV has evolved diverse strategies to modulate the type I interferon (IFN-I) response during infections. Recently, it has become increasingly recognized that microRNAs (miRNAs) can contribute to … Read more

J Immunol. 2026 May 14;215(5):vkag027. doi: 10.1093/jimmun/vkag027. ABSTRACT Immunological changes induced by a woman’s first pregnancy in controls and in cases of preeclampsia, which is more frequent and often a more severe complication in primigravid women, were investigated. Decidual natural killer (NK) cells are important for placentation and interact with HLA Ib molecules on extravillous … Read more

J Immunol. 2026 May 14;215(5):vkag102. doi: 10.1093/jimmun/vkag102. ABSTRACT The central nervous system (CNS) includes a uniquely regulated immune response that supports homeostasis, response to injury, and response to pathogens. Recent work has shown that virus-associated immune responses in the CNS may contribute to neuronal injury and long-term outcomes such as neurocognitive decline. However, the fundamental … Read more

J Immunol. 2026 May 14;215(5):vkag107. doi: 10.1093/jimmun/vkag107. ABSTRACT Both CD4+ and CD8+ T cells play critical roles in the immunopathogenesis of multiple sclerosis (MS). 1C6 T cell receptor transgenic (TcR-Tg) mice on the nonobese diabetic (NOD) background have a MOG[35-55] (myelin oligodendrocyte glycoprotein 35-55)-specific, major histocompatibility complex class II-restricted TcR that selects for both CD4+ … Read more

J Immunol. 2026 May 14;215(5):vkag106. doi: 10.1093/jimmun/vkag106. ABSTRACT For endemically circulating viruses, quantifying neutralization capacity of antibodies in a rapid and high-throughput manner is paramount given the ever-evolving targets of neutralization. Moreover, identifying features of an antibody response correlating with neutralization at the multivariate level can inform vaccine boosting strategies and next-generation monoclonal antibody therapies. … Read more

J Immunol. 2026 May 14;215(5):vkag112. doi: 10.1093/jimmun/vkag112. ABSTRACT Anti-CD19 chimeric antigen receptor (CAR) T cells have emerged as a promising therapeutic strategy for autoimmune diseases, including systemic lupus erythematosus. An unresolved question is how immunosuppressive preconditioning regimens influence CAR-T cell engraftment and therapeutic efficacy. In murine models, whole-body irradiation is required for optimal CAR-T cell … Read more

J Immunol. 2026 May 14;215(5):vkaf296. doi: 10.1093/jimmun/vkaf296. ABSTRACT CD8 cytolytic T cells are key players in fighting viral infections and other intracellular pathogens. In response to signals from the TCR, costimulatory molecules, and cytokines, CD8 T cells differentiate into populations of cytolytic effectors that can efficiently kill infected and tumor cells, as well as memory … Read more

J Immunol. 2026 May 14;215(5):vkag098. doi: 10.1093/jimmun/vkag098. ABSTRACT Coccidioidomycosis is a leading cause of pneumonia in the endemic area of the Sonora desert and the central valley of California. The causative agent are the fungi Coccidioides immitis and C. posadasii. While most infections ultimately resolve without treatment, some infections spread to the periphery and cause … Read more

J Immunol. 2026 May 14;215(5):vkag103. doi: 10.1093/jimmun/vkag103. ABSTRACT NFIL3 (E4BP4) is a basic leucine zipper transcription factor best known for its roles in circadian regulation. It functions primarily as a transcriptional repressor through competitive DNA binding and the recruitment of histone-modifying complexes. More recently, NFIL3 has emerged as a critical regulator of immunity. It is … Read more

J Immunol. 2026 May 14;215(5):vkag066. doi: 10.1093/jimmun/vkag066. ABSTRACT Neutrophils are crucial to innate immune responses to microbes. The engagement of opsonized pathogens by Fc gamma receptors (FcγRs) on neutrophil surfaces mediates multiple antimicrobial functions, including phagocytosis and the production of reactive oxygen species (ROS). FcγRIIIb (CD16b) is the most abundant FcγR on human neutrophils. This … Read more

J Immunol. 2026 May 14;215(5):vkag111. doi: 10.1093/jimmun/vkag111. ABSTRACT The cause of inflammatory bowel disease (IBD) is not known, but both innate and adaptive immunity contribute to IBD pathogenesis. To better understand the contributions of innate immunity to IBD, we have generated a mouse model of IBD that occurs spontaneously in the absence of adaptive immunity. … Read more

J Immunol. 2026 May 14;215(5):vkag002. doi: 10.1093/jimmun/vkag002. ABSTRACT Phosphoinositide 3-kinase (PI3K) mediates signaling downstream of many receptors expressed by B cells. Studies in both mice and humans have shown that PI3K plays a critical role in B-cell development, activation, and tolerance. Indeed the key role of PI3K in regulating activation versus tolerance is demonstrated by … Read more

J Immunol. 2026 May 14;215(5):vkag071. doi: 10.1093/jimmun/vkag071. NO ABSTRACT PMID:42153523 | DOI:10.1093/jimmun/vkag071

J Immunol. 2026 May 14;215(5):vkag075. doi: 10.1093/jimmun/vkag075. ABSTRACT Among the PI3K isoforms, PI3Kδ has attracted particular attention from immunologists and hematologists. Despite earlier clinical setbacks, the PI3Kδ field has recently re-emerged with renewed promise. Here, I highlight key milestones in the evolving understanding of PI3Kδ signaling in immunity and cancer, and pivotal studies that have … Read more

J Immunol. 2026 May 14;215(5):vkag085. doi: 10.1093/jimmun/vkag085. ABSTRACT NLRP3 inflammasome activation drives interleukin (IL)-1β and IL-18 cleavage and secretion and induces pyroptosis. The ketone body β-hydroxybutyrate (BHB), produced during metabolic stress such as caloric insufficiency, has been reported to inhibit this pathway. However, the conditions that enable this effect, and whether it extends to other … Read more

J Immunol. 2026 May 14;215(5):vkag097. doi: 10.1093/jimmun/vkag097. ABSTRACT While the majority of self-reactive CD4+ T cells are deleted or become Foxp3+ regulatory T cells during thymic development, some self-reactive conventional Foxp3- T cells escape to the secondary lymphoid organs early in life. The induction of anergy in such potentially autoreactive T cells has been proposed … Read more

J Immunol. 2026 May 14;215(5):vkag042. doi: 10.1093/jimmun/vkag042. ABSTRACT Nucleolar protein 16 (NOP16) has been increasingly implicated in promoting tumorigenesis and was recently identified as a novel epigenetic regulator. However, its physiological role in nonmalignant cells remains poorly understood. Although NOP16 is ubiquitously expressed across various tissues and cell types, we found it to be preferentially … Read more

J Immunol. 2026 May 14;215(5):vkag068. doi: 10.1093/jimmun/vkag068. ABSTRACT Lung tissue-resident CD8+ T cells facilitate viral clearance and protective immunity to influenza viruses in animal models. Their role during acute human infection is not clear. Here we use bronchoalveolar lavage samples collected from human subjects naturally infected with influenza B virus to show that influenza-specific CD8+ … Read more

J Immunol. 2026 May 14;215(5):vkag100. doi: 10.1093/jimmun/vkag100. ABSTRACT Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, is characterized by progressive renal inflammation and tissue injury. To define molecular mechanisms underlying LN progression, we analyzed temporal and spatial transcriptomic profiles in kidneys of lupus-prone New Zealand Black/White F1 mice at 10, 20, and 30 … Read more

J Immunol. 2026 May 14;215(5):vkag090. doi: 10.1093/jimmun/vkag090. ABSTRACT Alveolar macrophages (AMs) are key mediators of lung function and are potential targets for therapies during respiratory infections. TGFβ is an important regulator of AM differentiation and maintenance, but how TGFβ directly modulates the innate immune responses of AMs remains unclear. This shortcoming prevents effective targeting of … Read more

J Immunol. 2026 May 14;215(5):vkag065. doi: 10.1093/jimmun/vkag065. ABSTRACT As the most abundantly farmed freshwater fish species, grass carp (Ctenopharyngodon idella) faces a serious threat from Aeromonas hydrophila infection, underscoring the critical need to understand the genetic basis of disease resistance for selective breeding. This study deciphered the functional association and mechanism between polymorphisms in the … Read more

J Immunol. 2026 May 14;215(5):vkag070. doi: 10.1093/jimmun/vkag070. ABSTRACT During the response to infections and pathogenic challenges, T cells must expand profoundly and be resilient to repetitive restimulation to clear the ongoing assault and protect the host. This process of prolific expansion is tightly regulated to quickly provide a robust pool of pathogen-fighting T cells, yet … Read more

J Immunol. 2026 May 14;215(5):vkag096. doi: 10.1093/jimmun/vkag096. ABSTRACT Following acute viral infection, naïve CD4+ T cells differentiate into T helper 1 (Th1) and T follicular helper (Tfh) cells. The transcription factor Ets1 represses Tfh cell formation and function following protein immunization; however, whether Ets1 regulates Tfh differentiation in viral infection is unclear. Here, we demonstrate … Read more

J Immunol. 2026 Apr 15;215(4):vkag087. doi: 10.1093/jimmun/vkag087. ABSTRACT Monotherapies for lupus nephritis (LN) often fail to fully control the disease’s hallmark, renal inflammation and immune complex deposition. This study investigates a novel combination therapeutic strategy using urolithin A (UA), a multifaceted anti-inflammatory and antioxidant agent, with cyclosporine A (CsA), an established immunosuppressant. The combination therapy’s … Read more

J Immunol. 2026 Apr 15;215(4):vkag093. doi: 10.1093/jimmun/vkag093. ABSTRACT Major histocompatibility complex class II molecules present exogenous antigen-derived peptide to CD4+ T cells leading to T cell activation as well as signaling into the antigen-presenting cell. Class II is an αβ heterodimer that forms 2 distinct conformers via differential pairing of transmembrane domain GxxxG motifs (i.e. … Read more

J Immunol. 2026 Apr 15;215(4):vkag076. doi: 10.1093/jimmun/vkag076. ABSTRACT A large body of evidence indicates that Th17 cells play essential roles in mucosal immune responses and trigger autoimmune diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. Targeting Th17 cells holds promise for therapeutic innovation. While the core cytokine signaling networks driving Th17 differentiation have been … Read more

J Immunol. 2026 Apr 15;215(4):vkag077. doi: 10.1093/jimmun/vkag077. ABSTRACT Tissue-resident monocyte-lineage cells (TRMCs) are an extravascular population distinct from circulating monocytes and synovial macrophages and are critical for the development of inflammatory arthritis. However, the precise identities and origins of TRMC subpopulations remain unclear. Here, we characterize the ontogeny of TRMCs, which are comprised of bone … Read more

J Immunol. 2026 Apr 15;215(4):vkag086. doi: 10.1093/jimmun/vkag086. ABSTRACT Hematopoietic stem cell transplantation as treatment for patients with leukemia relies on chemotherapy and/or irradiation-based conditioning regimens to prevent graft rejection and cancer relapse. Despite advances in radiotherapy, total body irradiation for myeloablative conditioning is associated with dose and temporal heterogeneity, and how these variables impact thymus … Read more

J Immunol. 2026 Apr 15;215(4):vkag084. doi: 10.1093/jimmun/vkag084. ABSTRACT Plasma cells (PCs) are terminally differentiated B cells that are long-lived and have high rates of protein secretion. Because of these features, ex vivo generated PCs are being developed as therapeutics for long-term protein delivery. Here, we used proteomics and flow cytometry-based approaches to comprehensively interrogate the … Read more

J Immunol. 2026 Apr 15;215(4):vkag078. doi: 10.1093/jimmun/vkag078. ABSTRACT Genetically modified chimeric antigen receptor (CAR) T cells eliminate tumors by recognizing specific antigens on the cell surface. T cell ion channels (e.g. Kv1.3, KCa3.1) influence activation, proliferation, and effector functions such as target cell killing, through the regulation of Ca2+ signaling. We showed that CAR-expressing cells … Read more

J Immunol. 2026 Apr 15;215(4):vkag081. doi: 10.1093/jimmun/vkag081. ABSTRACT The innate immune system has evolved as the primary response mechanism against microbial infections, tissue damage, and cellular stress. Signals that disrupt homeostasis are sensed by pattern recognition receptors and initiate innate immune responses to restore homeostasis. Some intracellular pattern recognition receptors belonging to the Nod-like receptor, … Read more

J Immunol. 2026 Apr 15;215(4):vkag092. doi: 10.1093/jimmun/vkag092. ABSTRACT Emerging evidence from lupus-prone mice and patients with systemic lupus erythematosus implicates enhanced glycolysis in lymphocytes as a driver of disease. We previously showed that the pharmacologic blockade of glycolysis reduced the production of autoantibodies without affecting antibodies induced by immunization to a foreign protein. Here we … Read more

J Immunol. 2026 Apr 15;215(4):vkag088. doi: 10.1093/jimmun/vkag088. ABSTRACT Systemic lupus erythematosus (SLE) is a systemic autoimmune disease in which immune complexes (ICs) consisting of antinuclear autoantibodies (ANAs) and nuclear antigens induce complement activation and contribute to disease pathogenesis. The impact of antigen form on ICs formation and subsequent complement activation is not well understood. To … Read more

J Immunol. 2026 Apr 15;215(4):vkag073. doi: 10.1093/jimmun/vkag073. ABSTRACT Mucosal-associated invariant T (MAIT) cells are unconventional T cells, which upon activation can display potent cytotoxic and cytokine-producing capabilities. Together, these features make MAIT cells promising candidates for cancer immunotherapy. In this study, we show that MAIT cells can be efficiently amplified in vitro, and these amplified … Read more

J Immunol. 2026 Apr 15;215(4):vkag072. doi: 10.1093/jimmun/vkag072. ABSTRACT Ventricular arrhythmias are a primary cause of sudden cardiac death after acute myocardial infarction (AMI). Both β1-adrenergic autoantibodies (β1-AA) and nociceptin/orphanin FQ (N/OFQ) are implicated in AMI, but their potential interaction in ischemic arrhythmogenesis remains unclear. This study investigated the interplay between N/OFQ and β1-AA and the … Read more

J Immunol. 2026 Apr 15;215(4):vkag064. doi: 10.1093/jimmun/vkag064. ABSTRACT The immune system is a complex “network of networks,” where interactions between various immune cell subsets determine immune competence and influence disease onset or control. These interactions dictate whether the body remains in a healthy state or develops pathological conditions. Traditional statistical methods largely ignore these interactions … Read more

J Immunol. 2026 Apr 15;215(4):vkaf335. doi: 10.1093/jimmun/vkaf335. ABSTRACT Malaria remains a significant public health concern despite a steady decline in symptomatic cases. In Brazil, endemic regions are primarily concentrated in the Amazon region, where most cases are attributed to Plasmodium vivax. Although malaria does not confer long-term sterilizing immunity, clinical immunity is achieved, leading to … Read more

J Immunol. 2026 Apr 15;215(4):vkag089. doi: 10.1093/jimmun/vkag089. ABSTRACT Interleukin 22 (IL-22) produced by CD4+ T cells plays an important role in regulating intestinal immune responses during inflammation and infection, but the mechanisms controlling IL-22 expression in T cells remain incompletely understood. MicroRNA-10a (miR-10a) is known to regulate CD4+ T-cell function, but its role in IL-22 … Read more

J Immunol. 2026 Apr 15;215(4):vkag044. doi: 10.1093/jimmun/vkag044. ABSTRACT Salmonella Paratyphi A is a major cause of paratyphoid fever. Despite growing global concern, knowledge of S. Paratyphi A immunity remains limited, and no licensed vaccine exists. In a controlled human infection model (CHIM) homologous S. Paratyphi A rechallenge showed a non-significant reduction in risk of acute … Read more

J Immunol. 2026 Apr 15;215(4):vkag036. doi: 10.1093/jimmun/vkag036. ABSTRACT Natural killer (NK) cells are critical for early antiviral immunity, yet their metabolic regulation during acute human viral infection remains incompletely understood. We analyzed NK cell activation and metabolic reprogramming in 47 vaccinated individuals with mild breakthrough SARS-CoV-2 infection and 20 matched healthy control subjects. COVID-19 patients … Read more

J Immunol. 2026 Apr 15;215(4):vkag057. doi: 10.1093/jimmun/vkag057. ABSTRACT Chronic antibody-mediated kidney rejection (CABMR) is a major cause of chronic allograft injury. Fibroblasts have been implicated in mediating this injury through activation of the IL-6 amplifier loop (IL-6 + IL-17), driven by the NF-κB and STAT3 signaling pathways. This study investigated the activation of the IL-6 … Read more

J Immunol. 2026 Apr 15;215(4):vkag079. doi: 10.1093/jimmun/vkag079. ABSTRACT Neutrophils are usually the first cells recruited to sites of injury or infection where they mount antimicrobial responses, including the release of neutrophil extracellular traps (NETs). Toll-like receptors play a major role in the recognition of pathogen-associated molecular patterns and all but TLR3 are expressed in neutrophils. … Read more

J Immunol. 2026 Apr 15;215(4):vkag046. doi: 10.1093/jimmun/vkag046. ABSTRACT Transformed cells frequently adapt to immune pressure by modulating expression of ligands for PD-1 and CTLA-4. Despite the success of therapies targeting these interactions, only a minority of patients experience a clinical response, highlighting the critical need for alternative targets. Prior work from our group showed that … Read more

J Immunol. 2026 Apr 15;215(4):vkag048. doi: 10.1093/jimmun/vkag048. ABSTRACT Immunoglobulin class switch recombination by B lymphocytes requires the simultaneous expression of activation-induced cytidine deaminase (AID) and noncoding germline transcripts (GLT). Expression of both components is controllable through cytokine signalling and arise through stochastic mechanisms linked to cell division that can be predicted in mathematical models. Here … Read more

J Immunol. 2026 Apr 15;215(4):vkaf356. doi: 10.1093/jimmun/vkaf356. NO ABSTRACT PMID:42027188 | DOI:10.1093/jimmun/vkaf356

J Immunol. 2026 Apr 15;215(4):vkag043. doi: 10.1093/jimmun/vkag043. ABSTRACT CD4+ Th1 cells migrate to sites of inflammation, where they are indispensable for eliminating intracellular pathogens. The lineage-defining transcription factor T-bet establishes the T-helper 1 (Th1) transcriptional program, directing IFN-γ to drive effector responses and inducing subordinate transcription factors to shape the Th1 phenotype. Aberrant Th1 cell … Read more

J Immunol. 2026 Apr 15;215(4):vkag045. doi: 10.1093/jimmun/vkag045. ABSTRACT Interleukin 2 (IL-2) is a cytokine secreted by activated T cells that plays a central role in T cell proliferation and differentiation. In this study, we identified MARCH2, an E3 ubiquitin ligase of the MARCH family, as a negative regulator of IL-2 receptor alpha (IL-2Rα). MARCH2 interacts … Read more

J Immunol. 2026 Apr 15;215(4):vkag049. doi: 10.1093/jimmun/vkag049. ABSTRACT Autoimmune disorders reduce quality of life and lifespan and can increase B cell lymphoma risk. The adaptor protein TRAF3 regulates B cell survival, activation, and differentiation by restraining signaling through Toll-like receptors, tumor necrosis factor (TNF) receptor superfamily members, and the B cell antigen receptor-pathways linked to … Read more

J Immunol. 2026 Apr 15;215(4):vkag037. doi: 10.1093/jimmun/vkag037. ABSTRACT Escherichia coli (E. coli) is a leading cause of invasive bacterial infections in humans. Pathogenic E. coli is not only the major etiological agent of enteric/diarrheal disease and urinary tract infections, but also among the most common causes of sepsis and meningitis. Caspase-8 is known to regulate … Read more

J Immunol. 2026 Apr 15;215(4):vkag041. doi: 10.1093/jimmun/vkag041. ABSTRACT Riemerella anatipestifer infection causes septicemia and polyserositis in poultry, leading to serious economic losses to the global poultry industry. The ability to break through the host complement defense barrier is an important characteristic of R. anatipestifer. However, the underlying mechanisms are still not well understood at present. … Read more

J Immunol. 2026 Apr 15;215(4):vkag035. doi: 10.1093/jimmun/vkag035. ABSTRACT The importance of NAD metabolism in T cell differentiation and function has gained attention in recent years. However, technical limitations impede the specific interrogation of NAD dynamics in living immune cells. In this report, we present the redox index and capacity analysis (RICA) assay, a novel technique … Read more

J Immunol. 2026 Apr 15;215(4):vkaf371. doi: 10.1093/jimmun/vkaf371. ABSTRACT The immune environment at the maternal-fetal interface is highly regulated and changes depending on the stage of pregnancy. Any dysregulation or imbalance of the pro- and anti-inflammatory stages can disrupt placental development and can lead to various obstetric disorders, such as miscarriage, preterm birth, and preeclampsia. Several … Read more

J Immunol. 2026 Apr 15;215(4):vkag080. doi: 10.1093/jimmun/vkag080. ABSTRACT The Modular Immune In vitro Construct (MIMIC) system is an established laboratory-based methodology that reproduces in vitro the human in vivo T-cell immune response. In this study, we utilized the MIMIC system to establish a dendritic cell and CD4+ T-cell co-culture model that recapitulates T helper cell … Read more

J Immunol. 2026 Apr 15;215(4):vkag005. doi: 10.1093/jimmun/vkag005. ABSTRACT In this study, we investigate the mechanisms by which ischemia-free liver transplantation (IFLT) mitigates ischemia-reperfusion injury (IRI) and identify key therapeutic targets. Clinical data from 200 patients were collected to evaluate perioperative recovery and overall outcomes. Liver tissues were obtained from donors at the preprocurement, end-of-preservation, and … Read more

J Immunol. 2026 Apr 15;215(4):vkag063. doi: 10.1093/jimmun/vkag063. ABSTRACT The concept of polyfunctional secretion, the ability of cells to secrete multiple, functionally distinct proteins, has received increased attention for B cells as they have been described to secrete both antibodies and cytokines. However, the functional analysis of B cells was mostly performed in bulk, and consequently, … Read more

J Immunol. 2026 Apr 15;215(4):vkag054. doi: 10.1093/jimmun/vkag054. ABSTRACT Memory B cells (MBCs) are an integral part of the humoral immune response with the capacity to both reseed germinal center reactions and rapidly form antibody-secreting plasma cells (ASCs) upon secondary antigen encounter. MBCs arise via both T cell-dependent and -independent routes and while CD4+ T cells … Read more

J Immunol. 2026 Apr 15;215(4):vkag050. doi: 10.1093/jimmun/vkag050. ABSTRACT Group 3 innate lymphoid cells (ILC3s) preserve intestinal barrier integrity by producing IL-22 and IL-17A, yet the molecular mechanisms that maintain these cytokines during inflammation are incompletely defined. Here, we identify DAB2IP as a cell-intrinsic regulator of ILC3 effector function. In human inflammatory bowel disease mucosa, DAB2IP … Read more

J Immunol. 2026 Apr 15;215(4):vkag019. doi: 10.1093/jimmun/vkag019. ABSTRACT T cell immunity depends on the precise coordination of signaling networks with actin cytoskeleton remodeling, yet the molecular regulators of these processes remain incompletely defined. Flightless-1 (FLII) is a gelsolin-family actin regulator with unique leucine-rich repeats that can couple cytoskeletal dynamics to diverse signaling pathways. Here, using … Read more

J Immunol. 2026 Apr 15;215(4):vkag011. doi: 10.1093/jimmun/vkag011. ABSTRACT At the heart of Lyon, France, two leading institutes, the Centre International de Recherche en Infectiologie and the Cancer Research Center of Lyon, have built strong immunology programs since their establishment in the early 2010s. Their collaborative spirit led to the creation of the Immune Responses in … Read more

J Immunol. 2026 Apr 15;215(4):vkag059. doi: 10.1093/jimmun/vkag059. ABSTRACT Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid neoplasms characterized by treatment difficulties and a propensity to progress to acute myeloid leukemia. Impaired natural killer (NK) cell surveillance is a hallmark of MDS, yet the underlying molecular mechanisms remain poorly understood. This study aims to elucidate … Read more

J Immunol. 2026 Apr 15;215(4):vkag058. doi: 10.1093/jimmun/vkag058. ABSTRACT Peritoneal cavity (PerC) B cells can be classified into distinct subpopulations; however, their differential antigen-presenting capabilities and roles in antitumor immune responses remain largely unexplored. This study aimed to elucidate the properties of PerC B cell subpopulations in antitumor immune responses by using ovalbumin (OVA) peptides as … Read more

J Immunol. 2026 Apr 15;215(4):vkag038. doi: 10.1093/jimmun/vkag038. ABSTRACT T cells utilize diverse T cell receptors (TCRs) to recognize antigenic peptides and mediate adaptive immunity. However, the organization and function of αβ T cells in early vertebrates remain poorly understood. Here, we systematically characterized the TCRα locus and αβ T cell responses in Nile tilapia (Oreochromis … Read more

J Immunol. 2026 Apr 15;215(4):vkag062. doi: 10.1093/jimmun/vkag062. ABSTRACT CD8+ T-cell differentiation during chronic viral infection is supported by metabolic reprogramming to meet distinct bioenergetic demands. Early effector CD8+ T-cell differentiation and function are supported by the PI3K-Akt-mTOR pathway, while the differentiation of late exhausted CD8+ T cells remains incompletely understood. We first characterized the metabolic … Read more

J Immunol. 2026 Apr 15;215(4):vkag040. doi: 10.1093/jimmun/vkag040. ABSTRACT TLR20 is a teleost-specific TLR member. However, its species distribution, biological function, and underlying mechanism remain largely unknown. In this study, we systematically retrieved the TLR20 species distribution and found only a few teleosts contain different TLR20 variants, especially in Cyprinidae. Subsequently, we employed an economically important … Read more

J Immunol. 2026 Apr 15;215(4):vkag067. doi: 10.1093/jimmun/vkag067. ABSTRACT Negative regulators are crucial for maintaining immune homeostasis, yet the complexities of their regulatory mechanisms are not fully elucidated. In this study, we reveal that IGF2BP2, an m6A reader protein, orchestrates the formation of phase-separated condensates dependent on G3BP1, acting as a pivotal negative regulator of bacterial-induced … Read more

J Immunol. 2026 Apr 15;215(4):vkag056. doi: 10.1093/jimmun/vkag056. ABSTRACT Current immunotherapies for autoimmune diseases lack sufficient specificity and often compromise protective immunity, underscoring the need for precision-based approaches. Here, we identify x-mAb, a germline-encoded IgM autoantibody derived from dual-expresser lymphocytes of patients with type 1 diabetes (T1D), as a potent agent for precision immunotherapy. In the … Read more

J Immunol. 2026 Apr 15;215(4):vkag061. doi: 10.1093/jimmun/vkag061. ABSTRACT Neutrophils rapidly deploy phagocytosis, degranulation, and neutrophil extracellular trap (NET) formation to control infections, yet exaggerated NET formation contributes to tissue injury in inflammatory disease. Because NETosis is tightly linked to the cellular redox environment, we developed MorphoMapping, an imaging flow cytometry-based pipeline that resolves neutrophil morphotypes … Read more

J Immunol. 2026 Apr 15;215(4):vkaf376. doi: 10.1093/jimmun/vkaf376. ABSTRACT This study investigated the protective effect of miR-449b-5p from adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) targeting type 1 insulin-like growth factor receptor (IGF1R) on airway smooth muscle cells (ASMCs) and further investigated its mechanism of action. ADSC-Exos were isolated and characterized. Cellular uptake of ADSC-Exos by ASMCs … Read more

J Immunol. 2026 Apr 15;215(4):vkag028. doi: 10.1093/jimmun/vkag028. ABSTRACT The polarization of naive CD4+ T cells into Th2 cells is initiated in lymphoid organs and completed as the cells become tissue resident, where they express ST2, the receptor for the alarmin interleukin (IL)-33, which may be a key signal for tissue integration. Cellular metabolic requirements associated … Read more

J Immunol. 2026 Apr 15;215(4):vkag060. doi: 10.1093/jimmun/vkag060. ABSTRACT We have previously reported that T cells accumulate in the arteries of old mice and mechanistically contribute to the development of age-related arterial dysfunction. However, the specific T cell subtype that is the primary contributor to arterial aging is unknown. There is substantial evidence that CD8+ T … Read more

J Immunol. 2026 Apr 15;215(4):vkag053. doi: 10.1093/jimmun/vkag053. ABSTRACT Natural killer (NK) cells are key effectors of innate immunity and contribute to early control of viral infections. Their activity is regulated in part by interactions between killer cell immunoglobulin-like receptors (KIRs) on NK cells and major histocompatibility complex class I (MHC I) molecules on target cells. … Read more

J Immunol. 2026 Apr 15;215(4):vkag051. doi: 10.1093/jimmun/vkag051. ABSTRACT Folate receptor beta (FRβ), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FRβ as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR/Cas9-mediated gene deletion, we … Read more

J Immunol. 2026 Apr 15;215(4):vkaf357. doi: 10.1093/jimmun/vkaf357. NO ABSTRACT PMID:41984501 | DOI:10.1093/jimmun/vkaf357

J Immunol. 2026 Mar 17;215(3):vkag052. doi: 10.1093/jimmun/vkag052. ABSTRACT Pseudomonas aeruginosa (Pa) is an opportunistic pathogen threatening individuals with obesity, a condition associated with chronic meta-inflammation and altered immunity. In this study, we evaluate the immunogenicity and protective efficacy of a nanoemulsion-based subunit vaccine (L-PaF/ME/BECC) targeting Pa in a diet-induced obese mouse model. Mice fed a … Read more

J Immunol. 2026 Mar 17;215(3):vkaf372. doi: 10.1093/jimmun/vkaf372. ABSTRACT Microscale engagement of the hemi-immunoreceptor tyrosine-based activation motif-containing receptor Dectin-1 by fungal particles activates Src-family kinases (SFKs) and Syk, drives second-messenger generation, and induces downstream Erk and Akt signaling and proinflammatory responses in macrophages. To avoid inappropriate activation in the absence of a pathogenic threat, macrophages restrict … Read more