Journal of Immunology

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

J Immunol. 2025 Dec 12:vkaf298. doi: 10.1093/jimmun/vkaf298. Online ahead of print. ABSTRACT Pregnancy is characterized by dynamic immunological adaptations which are essential for maintaining both maternal and fetal health. The first-time use of coronavirus disease 2019 (COVID-19) vaccines in pregnant individuals presented an opportunity to discover pregnancy-specific immunoproteomic signatures across gestation. In this study, we … Read more

J Immunol. 2025 Dec 11:vkaf221. doi: 10.1093/jimmun/vkaf221. Online ahead of print. ABSTRACT Tristetraprolin (TTP) is an anti-inflammatory protein that mediates messenger RNA (mRNA) decay of certain transcripts, especially those encoding proinflammatory cytokines. TTP modulates various pathological outcomes in diverse inflammatory diseases; however, its role in ozone (O3)-induced acute lung injury (ALI) has never been tested. … Read more

J Immunol. 2025 Dec 10:vkaf297. doi: 10.1093/jimmun/vkaf297. Online ahead of print. ABSTRACT Enhancing regulatory T cell (Treg) function offers a compelling therapeutic strategy for autoimmune disease. Engineered IL-2 muteins selectively expand functional Tregs with minimal impact on other immune cells, but their potential to compromise antiviral immunity remains largely unexplored. Here, we used a murine … Read more

J Immunol. 2025 Dec 10:vkaf303. doi: 10.1093/jimmun/vkaf303. Online ahead of print. ABSTRACT Regulatory T cell (Treg)-biased IL-2/anti-IL-2 monoclonal antibody complexes (IL-2c) can preferentially deliver IL-2 to CD25+ Tregs, causing proliferation of Tregs that is potentially advantageous in transplantation. We tested the ability of IL-2c to prolong murine cardiac allograft survival. C57BL/6 (H-2b) mice received fully … Read more

J Immunol. 2025 Dec 8:vkaf325. doi: 10.1093/jimmun/vkaf325. Online ahead of print. ABSTRACT Freshwater crayfish as most aquatic crustaceans live for up to 20-30 years on the bottom of lakes and rivers, constantly exposed to millions of microorganisms. Consequently, they must have an effective immune system to combat and eliminate pathogens. The main immune cells are … Read more

J Immunol. 2025 Dec 6:vkaf302. doi: 10.1093/jimmun/vkaf302. Online ahead of print. ABSTRACT Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant pathogenic fungus that has rapidly spread across the world. Due to the high frequency of multidrug-resistant strains and mortality rate, C. auris is considered a critical health threat by the Centers for Disease Control … Read more

J Immunol. 2025 Dec 5:vkaf324. doi: 10.1093/jimmun/vkaf324. Online ahead of print. ABSTRACT Neutrophils are the first line of defense against fungal infection and other microbial pathogens. Through alternative pathway of complement activation in innate immunity, complement fragments (opsonin) generated promote phagocytosis of the yeast forms of fungal pathogens such as Candida albicans. However, when complement … Read more

J Immunol. 2025 Dec 3:vkaf310. doi: 10.1093/jimmun/vkaf310. Online ahead of print. ABSTRACT IgA-secreting plasma cells (PCs) provide durable humoral immunity by supplying critical antibodies to mucosal and systemic sites. These cells are found in large numbers in the gut lamina propria and the bone marrow (BM). In this study, we found that IgA+ PCs in … Read more

J Immunol. 2025 Dec 2:vkaf318. doi: 10.1093/jimmun/vkaf318. Online ahead of print. ABSTRACT Helper T cells (CD4 T cells) are lynchpins of adaptive immune responses. Each CD4 T cell expresses a single T-cell receptor, recognizing an epitope presented by major histocompatibility complex class II (MHC-II). Due to the enormous diversity of the T-cell repertoire, it is … Read more

J Immunol. 2025 Nov 29:vkaf290. doi: 10.1093/jimmun/vkaf290. Online ahead of print. ABSTRACT As the key component of the complement system, C3 plays important roles in complement activation to regulate phagocytosis, lyse cells, mediate inflammation, and clear immune complexes. In the present study, CgC3 in the cell-free hemolymph of the Pacific oyster Crassostrea gigas was found … Read more

J Immunol. 2025 Nov 1;214(11):2809-2811. doi: 10.1093/jimmun/vkaf232. ABSTRACT This Pillars of Immunology article is a commentary on “A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice,” a pivotal article written by Hao Y, O’Neill P, Naradikian MS, Scholz JL, and Cancro MP, and published in Blood in 2011 (PMID: 21562046; PMCID: PMC3152496). … Read more

J Immunol. 2025 Nov 25:vkaf323. doi: 10.1093/jimmun/vkaf323. Online ahead of print. ABSTRACT Janus kinase 2 (JAK2) has been linked to various neutrophil functions, but the intracellular mechanisms underlying its modulation are unknown. Neutrophils are essential cells for host defense. Neutrophil effector functions include migration, neutrophil extracellular trap production (NETosis), reactive oxygen species (ROS) production, and … Read more

J Immunol. 2025 Nov 25:vkaf320. doi: 10.1093/jimmun/vkaf320. Online ahead of print. ABSTRACT Organ transplantation is a life-saving treatment for patients with end-stage organ failure but requires lifelong immunosuppression that can result in significant complications. Achieving stable and durable donor-specific tolerance, whereby immunosuppression can be stopped without precipitating graft rejection, holds the promise to circumvent these … Read more

J Immunol. 2025 Nov 22:vkaf316. doi: 10.1093/jimmun/vkaf316. Online ahead of print. ABSTRACT The extracellular fibrinogen-binding protein (Efb) is one of nearly a dozen proteins secreted by Staphylococcus aureus to inhibit complement activation or amplification. The C-terminal domain of Efb (Efb-C) forms a high-affinity interaction with the thioester-containing domain of C3b (TED/C3d), thereby blocking formation of … Read more

J Immunol. 2025 Nov 20:vkaf312. doi: 10.1093/jimmun/vkaf312. Online ahead of print. ABSTRACT Peptide-based therapeutic vaccines exploit cross-presentation by dendritic cells for the induction of effective T cell responses. Their clinical success, however, has been limited due to incomplete understanding of antigen processing and presentation (APP). Bioorthogonal chemistry (BOC) uses chemical “click” reactions that can be … Read more

J Immunol. 2025 Nov 20:vkaf294. doi: 10.1093/jimmun/vkaf294. Online ahead of print. ABSTRACT The Mycobacterium tuberculosis complex (MTBC), comprising species such as M. tuberculosis, M. africanum, and M. canettii, is the causative agent of tuberculosis (TB), one of the deadliest infectious diseases worldwide. MTBC strains exhibit genetic diversity that influences host-pathogen interactions, immune evasion, and disease … Read more

J Immunol. 2025 Nov 18:vkaf314. doi: 10.1093/jimmun/vkaf314. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapy including immune checkpoint blockade (ICB). We previously showed that ICB selects for pancreatic tumor cells that are defective in IFN-γ-inducible MHC-I, prompting us to test the impact of IL-15 complex (IL-15C) in … Read more

J Immunol. 2025 Nov 16:vkaf287. doi: 10.1093/jimmun/vkaf287. Online ahead of print. ABSTRACT Assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the TCR repertoire’s diversity and the complexity of TCR-antigen recognition. We developed the peptide-driven identification of TCRs (PDI-TCR) assay that combines in vitro expansion of cells with peptide pools, bulk … Read more

J Immunol. 2025 Nov 15:vkaf311. doi: 10.1093/jimmun/vkaf311. Online ahead of print. ABSTRACT Interferon regulatory factors 3 and 7 (IRF3 and IRF7, respectively), which serve as key transcription factors in interferon (IFN) activation, are tightly regulated by a variety of mechanisms, including multiple posttranslational modifications, to fulfill their normal physiological functions. Nevertheless, the methylation-mediated regulation of … Read more

J Immunol. 2025 Nov 15:vkaf146. doi: 10.1093/jimmun/vkaf146. Online ahead of print. ABSTRACT Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that employs several strategies to evade the host immune system to establish a favorable niche inside the macrophages. One of the major immune evasion strategies involves induction of T helper 2 (Th2)-type response, which in turn … Read more

J Immunol. 2025 Nov 13:vkaf299. doi: 10.1093/jimmun/vkaf299. Online ahead of print. ABSTRACT Memory stem CD8+ T cells (TSCM) are a long-lived T-cell subset with stem cell-like properties, playing a key role in antiviral immunity. Despite their importance, comprehensive single-cell transcriptomic profiling of antigen-specific TSCM has not been previously conducted. In this study, an in vitro … Read more

J Immunol. 2025 Nov 11:vkaf301. doi: 10.1093/jimmun/vkaf301. Online ahead of print. ABSTRACT Antigen-specific responses to complex antigens encompass a range of cell states and reactivities to an array of epitopes, reflective of the heterogeneity in immune responses. Single-cell sequencing has created new opportunities when combined with flow cytometry for profiling of immune repertoire and cell … Read more

J Immunol. 2025 Nov 11:vkaf273. doi: 10.1093/jimmun/vkaf273. Online ahead of print. ABSTRACT Dendritic cells (DCs) and B lymphocytes produce major histocompatibility complex class II molecules (MHCIIs) in large amounts to maximize the display of peptides and fulfill their antigen-presentation functions. The surface expression of MHCIIs in these cells is regulated via the ubiquitination of a … Read more

J Immunol. 2025 Nov 11:vkaf306. doi: 10.1093/jimmun/vkaf306. Online ahead of print. ABSTRACT The sympathetic nervous system modulates immune responses through the release of norepinephrine (NE), yet the dynamics of this signaling differ across lymphoid organs. In this study, we investigated how NE release and α2-adrenergic receptor (α2AR) modulation influence neuroimmune interactions in the spleen and … Read more

J Immunol. 2025 Nov 11:vkaf309. doi: 10.1093/jimmun/vkaf309. Online ahead of print. ABSTRACT STAT3 is pivotal for governing myeloid responses to inflammatory stimuli to prevent hyperinflammation in vivo, yet whether STAT3 mediates pathogen control and clearance by myeloid cells remains unclear. In this study, we identified significant enrichment of IFN-stimulated transcriptional pathways in Stat3-deficient bone marrow-derived … Read more

J Immunol. 2025 Nov 10:vkaf292. doi: 10.1093/jimmun/vkaf292. Online ahead of print. ABSTRACT Artificial intelligence (AI) and machine learning (ML) are transforming biotechnology and playing a key role in bioeconomy. One of the most important measurement capabilities at the forefront of biotechnology innovations is flow cytometry (FCM), a high-throughput, single-cell analysis platform technology. However, the quality … Read more

J Immunol. 2025 Nov 10:vkaf300. doi: 10.1093/jimmun/vkaf300. Online ahead of print. ABSTRACT Mucosal immunoglobulin A (IgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating may be mediated by antigen-specific IgA recognition, polyreactivity, and/or by the IgA-associated glycans. We compared human polyclonal secretory SIgA both in vitro and in … Read more

J Immunol. 2025 Nov 9:vkaf260. doi: 10.1093/jimmun/vkaf260. Online ahead of print. ABSTRACT Mucosal-associated invariant T (MAIT) cells are highly conserved innate-like T cells in mammals recognized for their high baseline frequency in human blood and cytotoxic effector functions during infectious diseases, autoimmunity, and cancer. While the majority of these cells in humans express a conserved … Read more

J Immunol. 2025 Nov 9:vkaf280. doi: 10.1093/jimmun/vkaf280. Online ahead of print. ABSTRACT Cigarette smoke is the primary cause of chronic obstructive pulmonary disease (COPD), an incurable condition characterized by irreversible airflow obstruction and alveolar destruction driven by chronic inflammation of the lungs and airways. The inflammatory response caused by cigarette smoke is typified by the … Read more

J Immunol. 2025 Nov 6:vkaf218. doi: 10.1093/jimmun/vkaf218. Online ahead of print. ABSTRACT Increasing evidence indicates that invertebrates have the immune adaptive abilities, which is commonly known as “immune priming”. However, the mechanism of immune priming is believed to be rather complicated, and it has not been fully elucidated. In the present study, in the oysters … Read more

J Immunol. 2025 Nov 7:vkaf262. doi: 10.1093/jimmun/vkaf262. Online ahead of print. ABSTRACT Human whole blood (WB) immunophenotyping may represent the in vivo immunological state with better fidelity than artificially isolated peripheral blood mononuclear cells (PBMCs). We used a deep phenomics modeling approach to elucidate the quantitative differences in major immune cell lineages in WB and … Read more

J Immunol. 2025 Nov 4:vkaf293. doi: 10.1093/jimmun/vkaf293. Online ahead of print. ABSTRACT Activation of natural killer (NK) cells by transformed targets requires the engagement of activating receptors and commonly a concomitant loss of inhibitory signaling. While the coactivating receptor DNAM-1 is involved in NK cell recognition of tumors expressing the nectin-like molecule CD155, in many … Read more

J Immunol. 2025 Nov 3:vkaf295. doi: 10.1093/jimmun/vkaf295. Online ahead of print. ABSTRACT Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disorder triggered by pneumonia, sepsis, trauma, and COVID-19, leading to high mortality. In this study, we investigated the effect of aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent ligand, on LPS-induced … Read more

J Immunol. 2025 Nov 2:vkaf284. doi: 10.1093/jimmun/vkaf284. Online ahead of print. ABSTRACT FcɛR1γ is a transmembrane adaptor protein that regulates the activating receptors NKp30, NKp46, and CD16 expression and function in human natural killer (NK) cells. HLA-E expression by cancer cells suppresses NK cell function through interaction with NKG2A. Here, we engineered human NK cells … Read more

J Immunol. 2025 Nov 1:vkaf289. doi: 10.1093/jimmun/vkaf289. Online ahead of print. ABSTRACT Dimethyl fumarate (DMF) is an oral therapy approved for the treatment of relapsing-remitting multiple sclerosis, and it is known to reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Because self-reactive Th17 lymphocytes are thought to become activated in the gut before migrating to … Read more

J Immunol. 2025 Oct 31:vkaf250. doi: 10.1093/jimmun/vkaf250. Online ahead of print. ABSTRACT Cellular immunotherapy has revolutionized the treatment of hematologic malignancies yet has had limited success in the solid tumor microenvironment (TME). While insufficient nutrients can lead to T cell metabolic stress in the TME, the glutamine antagonist DON can paradoxically enhance antitumor immunity. Because … Read more

J Immunol. 2025 Oct 31:vkaf265. doi: 10.1093/jimmun/vkaf265. Online ahead of print. ABSTRACT Germinal centers (GCs) are specialized sites in lymphoid tissues where antigen-specific B cells undergo proliferation, affinity maturation, and differentiation into high-affinity memory B cells and long-lived plasma cells following immunization or infection. The specific signals and mechanisms that are involved in GC B … Read more

J Immunol. 2025 Oct 1;214(10):2523-2534. doi: 10.1093/jimmun/vkaf235. ABSTRACT Maternal immunity is critical for neonatal defense during early life, when infants are highly susceptible to infection. Antibodies transferred across the placenta or through breast milk not only provide immediate protection but also shape immune development. Defining the mechanisms and outcomes of this passive protection is essential … Read more

J Immunol. 2025 Oct 1;214(10):2494-2503. doi: 10.1093/jimmun/vkaf119. ABSTRACT While studies with laboratory rodent models have defined molecular and cellular components of the human immune system, experiments in these small mammals can’t capture all aspects of human immunity. This review focuses on immunologic research in large and agricultural species, highlighting how understanding immunity in a range … Read more

J Immunol. 2025 Oct 1;214(10):2515-2522. doi: 10.1093/jimmun/vkaf244. ABSTRACT Rodent models for evaluating new cancer immunotherapies often fail to fully recapitulate the complexity of immune interactions that occur in cancer patients. Companion dogs with spontaneously developing cancers more closely resemble humans immunologically than rodents. This resemblance results in part because their immune systems have been educated … Read more

J Immunol. 2025 Oct 1;214(10):2504-2514. doi: 10.1093/jimmun/vkaf231. ABSTRACT Infection of eastern North American woodchucks (Marmota monax) with woodchuck hepatitis virus (WHV) represents the most valuable immunopathogenic model of hepatitis type B that, like in humans, can advance stepwise from acute hepatitis to chronic hepatitis and hepatocellular carcinoma (HCC) or become self-resolving and persist as a … Read more

J Immunol. 2025 Oct 1;214(10):2489-2491. doi: 10.1093/jimmun/vkaf163. NO ABSTRACT PMID:41169233 | DOI:10.1093/jimmun/vkaf163

J Immunol. 2025 Oct 1;214(10):2535-2542. doi: 10.1093/jimmun/vkaf236. ABSTRACT While rodent models remain foundational in biomedical research for their manipulability, genetics, and reproducibility, spontaneous diseases in companion animals provide relevant models to study naturally occurring conditions. Pathogenic processes underlying diseases in humans and dogs are similar or identical, which exemplifies the One Health concept. Companion animals … Read more

J Immunol. 2025 Oct 1;214(10):2492-2493. doi: 10.1093/jimmun/vkaf238. NO ABSTRACT PMID:41169231 | DOI:10.1093/jimmun/vkaf238

J Immunol. 2025 Oct 30:vkaf276. doi: 10.1093/jimmun/vkaf276. Online ahead of print. ABSTRACT Influenza is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports showing an increased risk for cardiovascular disease. Studies have shown that influenza infection correlates with increased … Read more

J Immunol. 2025 Oct 30:vkaf263. doi: 10.1093/jimmun/vkaf263. Online ahead of print. ABSTRACT The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to … Read more

J Immunol. 2025 Oct 30:vkaf286. doi: 10.1093/jimmun/vkaf286. Online ahead of print. ABSTRACT The efficacy of seasonal influenza vaccines varies across age groups, even in individuals with strong antibody responses. Since protection against influenza virus infection also involves cellular immunity, identifying immune markers beyond neutralizing antibodies is crucial for informing the design of next-generation vaccines. Participants … Read more

J Immunol. 2025 Oct 30:vkaf271. doi: 10.1093/jimmun/vkaf271. Online ahead of print. ABSTRACT Septic peritonitis (SP) is a severe infectious complication associated with high morbidity and mortality. The role of microRNAs, particularly endothelial progenitor cell-derived exosomal miRNA-31 (EPC-ExosmiR-31), in modulating inflammatory pathways in SP has garnered scholars’ attention. However, its precise role and mechanism of action … Read more

J Immunol. 2025 Oct 29:vkaf277. doi: 10.1093/jimmun/vkaf277. Online ahead of print. ABSTRACT PTEN-induced kinase 1 (PINK1)-mediated mitophagy, a classic mechanism underlying the elimination of damaged mitochondria, plays a crucial role in the immune evasion of bacteria. In the present study, we found that Edwardsiella piscicida, an intracellular pathogenic bacterium that infects fish, could induce PINK1-mediated … Read more

J Immunol. 2025 Oct 29:vkaf258. doi: 10.1093/jimmun/vkaf258. Online ahead of print. ABSTRACT Endosomal toll-like receptors TLR7 and TLR8 are critical sensors of microbial RNA that initiate antiviral and antibacterial immune responses through type I interferon (IFN) and proinflammatory cytokine production. While TIRAP is traditionally associated with plasma membrane TLR signaling, recent evidence suggests that it … Read more

J Immunol. 2025 Oct 29:vkaf291. doi: 10.1093/jimmun/vkaf291. Online ahead of print. ABSTRACT The establishment of memory T cell responses is critical to protection against pathogens and is influenced by the conditions under which memory formation occurs. Iron is an essential micronutrient for multiple immunologic processes and nutritional deficiency is a common problem worldwide. Despite its … Read more

J Immunol. 2025 Oct 28:vkaf285. doi: 10.1093/jimmun/vkaf285. Online ahead of print. ABSTRACT The β2-adrenergic receptor (β2AR) signaling suppresses the activation of key inflammatory genes in Toll-like receptor (TLR) stimulated macrophages, but Il1b transcription is activated by β2AR signaling. The β2ARs potently activate protein kinase A and CREB, but other signaling pathways can also be activated, … Read more

J Immunol. 2025 Oct 28:vkaf288. doi: 10.1093/jimmun/vkaf288. Online ahead of print. ABSTRACT The risk of developing melanoma increases with age. Although immune checkpoint blockade (ICB) therapy has shown considerable success, a significant portion of melanoma patients either fail to respond to ICB or eventually develop resistance. This leads to the urgent need for exploring novel … Read more

J Immunol. 2025 Oct 28:vkaf279. doi: 10.1093/jimmun/vkaf279. Online ahead of print. ABSTRACT Natural killer (NK) cells play essential roles in immunity, but their limited infiltration into solid tumors restricts their therapeutic potential. Here, we identify fibroblast activation protein (FAP), previously thought to be largely fibroblast-restricted, as a novel surface-expressed protease on human NK cells. Using … Read more

J Immunol. 2025 Oct 25:vkaf275. doi: 10.1093/jimmun/vkaf275. Online ahead of print. NO ABSTRACT PMID:41139928 | DOI:10.1093/jimmun/vkaf275

J Immunol. 2025 Oct 25:vkaf264. doi: 10.1093/jimmun/vkaf264. Online ahead of print. ABSTRACT The liver contains a diverse repertoire of leukocytes, with liver B cells representing a significant population of hepatic immune cells in both newborns and adults. Despite their importance, these cells remain largely unexplored. In this study, we comprehensively characterized liver B cells from … Read more

J Immunol. 2025 Oct 23:vkaf256. doi: 10.1093/jimmun/vkaf256. Online ahead of print. ABSTRACT Highly immunodeficient BRGSF mice have proven to be suitable for reconstitution with human cord blood cell-derived CD34+ hematopoietic stem cells, enabling the generation of human immune system (HIS) mice. Here, we employ a robust comparative approach utilizing human lung biopsies to characterize the … Read more

J Immunol. 2025 Oct 23:vkaf270. doi: 10.1093/jimmun/vkaf270. Online ahead of print. ABSTRACT Nucleoporin 93 (Nup93), a key component of the nuclear pore complex, is involved in various cellular processes, such as immune signaling pathway. In mammals, Nup93 positively regulates the RLR signaling pathway by targeting TBK1 and IRF3. However, the role of Nup93 in teleost … Read more

J Immunol. 2025 Oct 17:vkaf274. doi: 10.1093/jimmun/vkaf274. Online ahead of print. ABSTRACT Sarcoidosis is a granulomatous systemic inflammatory disease predominantly affecting the lungs. It shares histopathological, clinical, and immune features with tuberculosis (TB). There are currently no diagnostic tests to formally identify sarcoidosis; instead, there is a need first to rule out the presence of … Read more

J Immunol. 2025 Oct 16:vkaf281. doi: 10.1093/jimmun/vkaf281. Online ahead of print. ABSTRACT DDX3 and other DEAD-box RNA helicases regulate nuclear export, translation, splicing, and metabolism of RNA. Perturbation of Ddx3x on the mouse X-chromosome in all hematopoietic cells resulted in a loss of natural killer (NK) cells, yet whether DDX3X is important only in progenitors … Read more