Journal of Immunology

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

J Immunol. 2026 Mar 17;215(3):vkag039. doi: 10.1093/jimmun/vkag039. ABSTRACT Co-inhibitory receptors are essential checkpoints to restrain excessive T cell activation. While PD1 and CTLA4 have been extensively studied, the biology of lymphocyte activation gene 3 (Lag3), an emerging target for checkpoint blockade immunotherapy, remains less understood. In this study, we show that Lag3, though largely intracellular … Read more

J Immunol. 2026 Mar 17;215(3):vkag016. doi: 10.1093/jimmun/vkag016. ABSTRACT Neutrophils infiltrate lesional skin robustly in individuals with psoriasis. However, their role in chronically inflamed skin-particularly in terms of phenotypic and functional diversity-remains poorly understood. In this study, we investigated the functional potential of 2 distinct circulating neutrophil populations-conventional, polymorphonuclear neutrophils (cNeu) and low-density neutrophils (LDNeu)-to infiltrate … Read more

J Immunol. 2026 Mar 17;215(3):vkag021. doi: 10.1093/jimmun/vkag021. ABSTRACT Community-acquired pneumonia (CAP) poses a serious threat to the lives of adults. Differentially expressed miRNAs play a crucial regulatory role in CAP. This study aims to explore the diagnostic and prognostic significance of miR-4492 in CAP and its possible mechanism of action with tumor necrosis factor receptor-associated … Read more

J Immunol. 2026 Mar 25;215(S3):vkag023. doi: 10.1093/jimmun/vkag023. ABSTRACT While multiple sclerosis research has long centered on focal demyelinating lesions, it is increasingly recognized that there are distinct, surface-in gradients of diffuse pathology that exist in regions abutting the cerebrospinal fluid (CSF), such as the subpial cortex and periventricular parenchyma. While subpial pathology is thought to … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf267. doi: 10.1093/jimmun/vkaf267. ABSTRACT The skull bone marrow (sBM) is a hematopoietic site intimately connected to the dura mater-the outermost layer of the meninges that surround the central nervous system (CNS)-via vascular channels that enable trafficking of immune cells and sampling of cerebrospinal fluid. sBM-derived cells directly access the dura under … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf321. doi: 10.1093/jimmun/vkaf321. ABSTRACT The retina is a central nervous system tissue with immune-privileged status, protected by the blood-retina barrier and maintained by specialized resident tissue macrophages: microglia, hyalocytes, and perivascular macrophages. These cells exhibit specific ontogeny, spatial localization, and immunologic functions. Each population contributes to homeostasis, phagocytosis, and immunoregulation in … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf344. doi: 10.1093/jimmun/vkaf344. ABSTRACT The outer layer of the meninges, the dura mater, forms a critical interface at the border of the central nervous system (CNS). While historically the dura was viewed as a protective physical barrier for the brain and spinal cord, providing structural support for the venous sinuses, more … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf337. doi: 10.1093/jimmun/vkaf337. ABSTRACT Body-brain neuroimmune signaling is important for maintaining homeostasis and behavior. Dysregulation of these interoceptive communication pathways leads to compromised physical and mental health often associated with psychiatric disorders. Specialized interoceptive nodes considered as “gateways” to the brain offer an interface for communication with the periphery to aid … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf308. doi: 10.1093/jimmun/vkaf308. ABSTRACT Subdural central nervous system (CNS)-associated macrophages (CAMs), encompassing macrophages of the leptomeninges and perivascular spaces, serve as the primary immune sentinels at the CNS interfaces. These cells have been suggested to be indispensable for maintaining homeostasis and orchestrating responses in pathological states. Under physiological conditions, CAMs continuously … Read more

J Immunol. 2026 Mar 25;215(S3):vkag003. doi: 10.1093/jimmun/vkag003. ABSTRACT Fibroblasts in the central nervous system (CNS) are restricted to the organ’s borders, providing mechanical protection, barrier functions, and an infrastructure for the pervading vasculature. An immunological function for these cells has not been considered until recently. In the last decade, new insights into CNS immune surveillance, … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf326. doi: 10.1093/jimmun/vkaf326. ABSTRACT Olfaction, or the sense of smell, is the ability to detect airborne chemicals that transmit environmental information. Evolutionarily, this sense is essential for finding and judging the safety of food, mediating social relationships, marking territory, and assessing danger. In humans, olfaction is commonly thought to have a … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf322. doi: 10.1093/jimmun/vkaf322. ABSTRACT The choroid plexus (ChP) is increasingly recognized as a dynamic neuroimmune interface that integrates peripheral and central signals to regulate cerebrospinal fluid (CSF) homeostasis, leukocyte trafficking, and inflammatory tone within the central nervous system (CNS). Recent studies reveal that beyond their classic roles in CSF production and … Read more

J Immunol. 2026 Mar 25;215(S3):vkaf338. doi: 10.1093/jimmun/vkaf338. NO ABSTRACT PMID:41876362 | DOI:10.1093/jimmun/vkaf338

J Immunol. 2026 Mar 17;215(3):vkag033. doi: 10.1093/jimmun/vkag033. ABSTRACT Interleukin 1-beta (IL-1β) is an inflammatory cytokine produced by myeloid cells in response to infection or sterile tissue damage. Secretion of bioactive IL-1β from macrophages (Mφ) or dendritic cells (DC) downstream of activated NLRP3/caspase-1 inflammasomes is the best characterized model; this is mediated by caspase-1 cleavage of … Read more

J Immunol. 2026 Mar 17;215(3):vkag009. doi: 10.1093/jimmun/vkag009. ABSTRACT Echoviruses commonly infect humans and can cause severe outcomes, including meningitis and liver failure, especially in neonates and immunocompromised individuals. Although recent progress has been made in understanding acute pathogenesis and innate immunity to echoviruses, adaptive immune responses remain poorly defined, in part due to the lack … Read more

J Immunol. 2026 Mar 17;215(3):vkag001. doi: 10.1093/jimmun/vkag001. ABSTRACT The traditional view of the immune system distinguishes between the innate immune system, which serves as the host’s first line of defense against pathogens, and the adaptive immune system, which evolved to manage more complex or recurrent infections. However, the discovery of evolutionarily conserved mechanisms in innate … Read more

J Immunol. 2026 Mar 19:vkag022. doi: 10.1093/jimmun/vkag022. Online ahead of print. ABSTRACT The Syrian hamster (Mesocricetus auratus) is an important model for human infectious diseases, particularly those that infect the respiratory tract, due to having similar disease progression and immune responses as humans. However, immune repertoire studies are extremely limited due to incomplete genomic characterization … Read more

J Immunol. 2026 Mar 17;215(3):vkag013. doi: 10.1093/jimmun/vkag013. ABSTRACT Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen-specific (TAS) CD8+ tumor-infiltrating lymphocytes … Read more

J Immunol. 2026 Mar 17;215(3):vkag026. doi: 10.1093/jimmun/vkag026. ABSTRACT Tumor-associated macrophages are an abundant, tumor-infiltrating cell population that supports the evasion of tumor cells from antitumoral immune cell detection by generating an immunosuppressive tumor-immune microenvironment (TIME). The immunosuppressive function of macrophages is dictated by the cytokine environment. IL-9 is a pleiotropic cytokine that can be a … Read more

J Immunol. 2026 Mar 17;215(3):vkag029. doi: 10.1093/jimmun/vkag029. ABSTRACT Autophagy serves as a crucial defense mechanism against Mycobacterium tuberculosis (Mtb) survival within infected macrophages. Transcription factor EB (TFEB) and upstream stimulatory factor 2 (USF2) belong to the bHLH-Zip family and regulate the transcription of autophagy-related genes, thereby modulating host-pathogen interactions. However, the mechanisms by which Mtb … Read more

J Immunol. 2026 Mar 17;215(3):vkag020. doi: 10.1093/jimmun/vkag020. ABSTRACT Asthma is a chronic airway disease driven by type 2 immune responses, a core mechanism shared across allergic conditions. Cathepsins (CTSs), lysosomal proteases that regulate immune processes such as autophagy, antigen presentation, and cytokine modulation, have been implicated in allergy, but whether specific CTSs-particularly cathepsin B (CTSB)-causally … Read more

J Immunol. 2026 Mar 17;215(3):vkag014. doi: 10.1093/jimmun/vkag014. ABSTRACT The fetomaternal interface (FMi), comprising fetal chorionic trophoblast cells (CTCs) and maternal decidual stromal cells (DECs), plays a critical role in providing immune tolerance during pregnancy. Intrauterine inflammation is major trigger of adverse outcomes such as preterm birth, yet the cell-specific inflammatory responses at the FMi -; … Read more

J Immunol. 2026 Mar 17;215(3):vkag025. doi: 10.1093/jimmun/vkag025. ABSTRACT Antibodies are secreted by specialized antibody-secreting cells, also known as plasma cells (PCs), which differentiate from antigen-activated B cells. Antibodies are critical for protection against many types of infection and are correlates of vaccine efficacy. Iron metabolism is important for antibody responses, and heme (the major source … Read more

J Immunol. 2026 Mar 17;215(3):vkag034. doi: 10.1093/jimmun/vkag034. ABSTRACT N6-methyladenosine (m6A) represents a reversible and ubiquitous posttranscriptional modification of mRNA. It plays a crucial role in immune cell development and is implicated in a range of pathological conditions. Nevertheless, the precise role of m6A in LPS-induced macrophage inflammatory responses remains elusive. In the present study, we … Read more

J Immunol. 2026 Mar 17;215(3):vkag017. doi: 10.1093/jimmun/vkag017. ABSTRACT Chemokines play a crucial role in the lung’s immune responses to infections and diseases. The role of CXC ligand 13 (CXCL13), a chemokine produced homeostatically by various lung cell types, in protecting against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease remains controversial. Some studies … Read more

J Immunol. 2026 Mar 17;215(3):vkag015. doi: 10.1093/jimmun/vkag015. ABSTRACT Histone deacetylase HDAC7 is required for early B cell development and governs the acquisition of B cell progenitors gene identity. Its role in mature B cell biology and associated malignancies is unknown. Here, by using a conditional mouse model for specific deletion in activated B cells, we … Read more

J Immunol. 2026 Mar 17;215(3):vkag018. doi: 10.1093/jimmun/vkag018. ABSTRACT Acute hepatopancreatic necrosis disease (AHPND) is one of the most severe threats to global shrimp aquaculture. Recent studies report a significant reduction in hepatopancreas hemocyanin levels in Penaeus vannamei (PvHMC) by AHPND. To investigate the functional implications, we performed liquid chromatography-tandem mass spectrometry-based metabolomics and found that … Read more

J Immunol. 2026 Mar 17;215(3):vkaf361. doi: 10.1093/jimmun/vkaf361. ABSTRACT Infants are significantly more susceptible to respiratory infection, often resulting in increased morbidity and hospitalization, and occasionally death. This susceptibility is partially explained by the developing nature of the thymus in human infants at-and for several months after-birth. However, the contribution of T cells produced in this … Read more

J Immunol. 2026 Feb 9;215(2):vkaf304. doi: 10.1093/jimmun/vkaf304. ABSTRACT Viral infections remain a challenge to aquaculture, resulting in severe economic losses and threatening fish health worldwide. As a key immunomodulatory and antiviral factor, interferon (IFN) plays a crucial role in regulating immune responses. We constructed a high-level expression strain of recombinant interferon (Rec-IFN) using Synechococcus sp. … Read more

J Immunol. 2026 Feb 9;215(2):vkaf366. doi: 10.1093/jimmun/vkaf366. ABSTRACT Epstein-Barr virus (EBV) is a human γ-herpesvirus that establishes latency and lifelong infection in B cells. Failure to control latent EBV infection can result in a variety of malignancies, including lymphoproliferative diseases. Studies have implicated natural killer (NK) cells as critical in the host defense against lytic … Read more

J Immunol. 2026 Feb 9;215(2):vkaf368. doi: 10.1093/jimmun/vkaf368. ABSTRACT Negative T-cell regulation through programmed cell death 1 (PD-1)-programmed death ligand 1 (PD-L1) ligation is well described during viral infection; however, our understanding of the contribution of PD-L1-intrinsic signaling to antiviral immunity is limited. Herein, we show that mutation of the PD-L1 intracellular domain results in a … Read more

J Immunol. 2026 Feb 9;215(2):vkag006. doi: 10.1093/jimmun/vkag006. ABSTRACT Adipocytes accumulate in the bone marrow with age. This has been proposed to trigger age-related changes in hematopoiesis that include a decline in B cell development. Bone marrow fat cells differ from adipocytes in other areas of the body and include 2 subsets termed constitutive and regulated … Read more

J Immunol. 2026 Feb 9;215(2):vkaf360. doi: 10.1093/jimmun/vkaf360. ABSTRACT Toxoplasma gondii is an obligate intracellular pathogen that can infect most nucleated cell types in rodents and humans. Parasite infection is regulated by inflammasome activation, downstream of Toll-like receptors (TLRs) priming, and interferon γ (IFN-γ)-mediated activation of immunity inducible GTPases. In vivo, the activation of these pathways … Read more

J Immunol. 2026 Feb 9;215(2):vkaf363. doi: 10.1093/jimmun/vkaf363. ABSTRACT Mast cells are tissue-resident granulocytes that are often viewed through a negative lens due to their roles in allergies and hypersensitivity. While central to these conditions, mast cells have broader roles in vertebrate immune systems that are often overlooked. Whereas most mast cell research to date has … Read more

J Immunol. 2026 Feb 9;215(2):vkaf358. doi: 10.1093/jimmun/vkaf358. ABSTRACT Soil-transmitted helminths are one of the most common infections globally, yet how to promote effective gut-associated humoral responses is not well understood. We identify the histone methyltransferase MLL1 as a key target to promote IgA-driven responses. Mll1 was increased in germinal center B cells in gut-associated lymphoid … Read more

J Immunol. 2026 Feb 9;215(2):vkaf347. doi: 10.1093/jimmun/vkaf347. ABSTRACT Type 1 diabetes (T1D) is a genetic autoimmune disease in children and young adults, with no cure, emphasizing the need for novel genetic-based therapies. Differential analysis using the “Limma” package identified 42 upregulated genes in the peripheral blood of T1D patients. Gene Ontology/Kyoto Encyclopedia of Genes and … Read more

J Immunol. 2026 Feb 9;215(2):vkaf340. doi: 10.1093/jimmun/vkaf340. ABSTRACT This study elucidates the regulatory role and molecular mechanism of the circular RNA actin-related protein 2 homolog (circACTR2) in macrophage phenotypic transformation and renal injury in chronic kidney disease (CKD). A mouse model of CKD was established via adenine administration. An in vitro inflammatory model was generated … Read more

J Immunol. 2026 Feb 9;215(2):vkaf370. doi: 10.1093/jimmun/vkaf370. ABSTRACT This study aimed to investigate the role of CD29 and CD99 in human T lymphocytes and elucidate its significance in Sjögren’s disease (SjD). ScRNA-Seq data were utilized to analyze CD29 and CD99 expression in PBMCs. CD29 and CD99-expressing T lymphocyte proportions in SjD patients and healthy controls … Read more

J Immunol. 2026 Feb 9;215(2):vkaf381. doi: 10.1093/jimmun/vkaf381. ABSTRACT Type 1 diabetes (T1D) is an autoimmune disease in which T cells mediate the elimination of the insulin-producing beta cells in the pancreatic islets, resulting in the need for exogenous insulin. Studies of T1D in both patients and the nonobese diabetic (NOD) mouse model of the disease … Read more

J Immunol. 2026 Feb 9;215(2):vkaf327. doi: 10.1093/jimmun/vkaf327. ABSTRACT Glioblastoma (GBM) remains the most lethal intracranial malignancy in the central nervous system with limited therapeutic options. Laser interstitial thermal therapy (LITT) has emerged as a novel minimally invasive treatment for GBM. Around the core ablation zone of LITT, there exists a sublethal ablation zone caused by … Read more

J Immunol. 2026 Feb 9;215(2):vkaf350. doi: 10.1093/jimmun/vkaf350. ABSTRACT Co-expression of 2 T cell receptor (TCR) clonotypes due to allelic inclusion occurs in ∼16% of peripheral blood T cells in mice and humans. Evidence indicates dual TCR expression can affect thymic development and peripheral function. Notably, dual TCR cells demonstrate increased reactivity against self-antigens and heightened … Read more

J Immunol. 2026 Feb 9;215(2):vkaf346. doi: 10.1093/jimmun/vkaf346. ABSTRACT MR1 is an major histocompatibility complex class I-like molecule that presents small molecule metabolites to MR1-restricted T cells that include a major population of highly conserved T cells known as mucosal-associated invariant T (MAIT) cells. MAIT cells recognize bacterial riboflavin pathway-derived neoantigens and are being attributed an … Read more

J Immunol. 2026 Feb 9;215(2):vkaf367. doi: 10.1093/jimmun/vkaf367. ABSTRACT Dickkopf1 (DKK1) is a quintessential Wnt antagonist and immunomodulator in various inflammatory diseases. The underlying molecular mechanisms of DKK1-mediated immunomodulation remain elusive. Here, we identified TLR4 as a new receptor for DKK1, activating NFκB-mediated gene expression. Subsequently, this event resulted in pyroptosis via the NLRP3 inflammasome in … Read more

J Immunol. 2026 Feb 9;215(2):vkaf359. doi: 10.1093/jimmun/vkaf359. ABSTRACT Membrane atg8ylation is a broad homeostatic process of immunological import. It encompasses membrane repair and remodeling pathways, including canonical autophagy, in cells subjected to stress, damage, infection, and immune or metabolic signaling under microbe-induced or sterile inflammatory conditions. The initial reports on autophagy, which is one of … Read more

J Immunol. 2026 Feb 9;215(2):vkaf331. doi: 10.1093/jimmun/vkaf331. ABSTRACT Exposure to a diversity of microbes has been implicated in playing a major role in susceptibility to the development of allergic lung-type diseases. The hygiene hypothesis suggests that those exposed to a broad diversity of microbes are more likely to be protected against developing allergic-type diseases. However, … Read more

J Immunol. 2026 Feb 9;215(2):vkaf341. doi: 10.1093/jimmun/vkaf341. ABSTRACT Preterm birth is the leading cause of neonatal morbidity and mortality. Management of preterm labor relies on the use of tocolytics, like nifedipine, which fail to prevent preterm birth and related morbidities. Interleukin-1β plays significant roles in the pathophysiology of preterm birth including inflammation and uterine activation. … Read more

J Immunol. 2026 Feb 9;215(2):vkaf362. doi: 10.1093/jimmun/vkaf362. ABSTRACT Environmental temperature significantly influences immune responses. Cold exposure suppresses host defense against infections and exacerbates autoimmune and allergic conditions. However, the molecular mechanisms underlying temperature-dependent immune regulation remain unclear. In this study, we evaluated the cold-activated sympathetic modulation of immune responses. We presented that semaphorin 6D (Sema6D), … Read more

J Immunol. 2026 Feb 9;215(2):vkaf351. doi: 10.1093/jimmun/vkaf351. ABSTRACT Sepsis-induced liver injury involves profound immune dysregulation. Natural compounds such as artesunate (ART), capsaicin (CAP), and oridonin (ORI) have demonstrated efficacy in mitigating systemic inflammation; however, their comparative cellular mechanisms in sepsis remain poorly characterized. Here, we integrated and reanalyzed the single-cell transcriptomic datasets of murine livers … Read more

J Immunol. 2026 Jan 21;215(1):vkaf222. doi: 10.1093/jimmun/vkaf222. ABSTRACT During the progression of acetaminophen (N-acetyl-para-aminophenol [APAP])-induced liver injury, the innate immune response is implicated in the induction of tissue damage. However, the precise cellular and molecular mechanisms underlying this process are not yet completely elucidated. CARD9 is known to modulate the activation of the NF-κB family … Read more

J Immunol. 2025 Dec 28:vkaf349. doi: 10.1093/jimmun/vkaf349. Online ahead of print. ABSTRACT Coronin family proteins are involved in various cellular processes, such as actin cytoskeleton reorganization, cell motility, and vesicular trafficking. Coronin-1, encoded by Coro1a, is specifically expressed in immune cells, and its defect causes severe immunodeficiencies. However, the regulatory mechanisms of Coro1a expression in … Read more

J Immunol. 2025 Dec 27:vkaf330. doi: 10.1093/jimmun/vkaf330. Online ahead of print. ABSTRACT Type 1 diabetes (T1D) results from immune-mediated destruction of pancreatic beta cells. B cells serve as critical antigen-presenting cells whose autoreactive specificities drive disease progression. Conversely, IL-10 producing regulatory B cells (Bregs) exert immunosuppressive functions and have been shown to protect against autoimmunity … Read more

J Immunol. 2025 Dec 25:vkaf315. doi: 10.1093/jimmun/vkaf315. Online ahead of print. ABSTRACT Previous studies have reported that African swine fever virus (ASFV) infection can induce inflammatory responses through the activation of the NLRP3 inflammasome, resulting in the release of IL-1β and the cleavage of gasdermin D. However, the mechanism by which pattern recognition receptors in … Read more

J Immunol. 2025 Dec 25:vkaf305. doi: 10.1093/jimmun/vkaf305. Online ahead of print. ABSTRACT The SARS-CoV-2 pandemic underscored the need for innovative approaches to study humoral immunity and isolate monoclonal antibodies (mAbs) with diagnostic and therapeutic potential. Current methods for repertoire analysis at the clonal level require large-scale recombinant mAb production, limiting accessibility and delaying functional insight. … Read more

J Immunol. 2025 Dec 22:vkaf319. doi: 10.1093/jimmun/vkaf319. Online ahead of print. ABSTRACT The innate immune system of teleost fish, such as Takifugu obscurus, depends on pattern recognition receptors to detect microbes and mount immune responses. In this study, a new collectin gene was identified in T. obscurus, designated ToCL-11. The full-length cDNA of ToCL-11 encodes … Read more

J Immunol. 2025 Dec 13:vkaf328. doi: 10.1093/jimmun/vkaf328. Online ahead of print. ABSTRACT B cells play critical roles in humoral immunity to infection, vaccination, and autoimmunity. The differentiation of B cells into antibody-producing plasma cells (PCs) has been extensively studied, but the role of metabolic transporters that mediate nutrient uptake during PC differentiation is not well-understood. … Read more

J Immunol. 2025 Dec 13:vkaf169. doi: 10.1093/jimmun/vkaf169. Online ahead of print. ABSTRACT Chronic graft-versus-host disease (cGVHD) develops with complex interactions between immune cells and cytokines, leading to irreversible fibrosis. Severe cGVHD impairs quality of life and is associated with nonrelapse mortality; however, effective treatments are limited. Recombinant human soluble thrombomodulin (rTM), a novel anticoagulant consisting … Read more

J Immunol. 2025 Dec 12:vkaf317. doi: 10.1093/jimmun/vkaf317. Online ahead of print. ABSTRACT Human macrophages (MΦs) reside in tissues and develop tissue-specific identities. While studies in mice have identified molecular signatures for site-specific MΦ differentiation, less is known about the transcriptional profiles of human MΦs in distinct sites, including mucosal tissues and lymphoid organs during homeostasis … Read more