Journal of Immunology

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

J Immunol. 2025 Oct 16:vkaf278. doi: 10.1093/jimmun/vkaf278. Online ahead of print. ABSTRACT Eukaryotic elongation factor 2 kinase (eEF2K) is a stress-responsive regulator of protein synthesis implicated in melanoma progression, but its role in tumor immune evasion remains poorly defined. We investigated how eEF2K influences programmed death ligand 1 (PD-L1) expression through modulation of Cyclin D1. … Read more

J Immunol. 2025 Oct 14:vkaf225. doi: 10.1093/jimmun/vkaf225. Online ahead of print. ABSTRACT Impaired phagocytosis of macrophages was observed in the salivary glands (SGs) of Sjogren’s syndrome (SS). This study aims to investigate the dynamic changes of extracellular high mobility group box 1 (HMGB1) within these tissue microenvironments and its roles in macrophage function and subsequent … Read more

J Immunol. 2025 Oct 15:vkaf158. doi: 10.1093/jimmun/vkaf158. Online ahead of print. ABSTRACT Pinctada fucata martensii is an economically important mollusk in aquaculture, known for marine pearl production. The inflammatory response during the transplantation process was a key factor affecting pearl yield. Our previous studies have revealed the critical role of nicotinic acetylcholine receptors (nAChRs) from … Read more

J Immunol. 2025 Oct 13:vkaf282. doi: 10.1093/jimmun/vkaf282. Online ahead of print. ABSTRACT B cells have been shown to be phagocytic under some circumstances. However, the phagocytic capacity of different B-cell subsets and how this is linked to antigen (Ag) presentation or other functions has not been characterized. To address this, we developed 2-µm phagocytic Ag-conjugated … Read more

J Immunol. 2025 Oct 12:vkaf249. doi: 10.1093/jimmun/vkaf249. Online ahead of print. ABSTRACT Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions systemic responses are poorly understood. Here, we leveraged a highly compartmentalized model of skin inflammation and identified a surprising type I interferon (IFN)-mediated activation of hematopoietic stem/progenitor … Read more

J Immunol. 2025 Oct 10:vkaf268. doi: 10.1093/jimmun/vkaf268. Online ahead of print. ABSTRACT Tuberculosis (TB) is a major global health threat. Deep knowledge of the immune responses against Mycobacterium tuberculosis (Mtb) is crucial for developing effective interventions. Data support that both innate and adaptive CD8+ lymphocytes contribute to protective immunity in Mtb infections, commonly attributed to … Read more

J Immunol. 2025 Oct 10:vkaf214. doi: 10.1093/jimmun/vkaf214. Online ahead of print. ABSTRACT Memory CD8+ T cells are essential for long-term protective immunity. Here, we show that activation of p38 MAPK during the primary response of CD8+ T cells orchestrates a delicate balance between the formation of short-lived effector cells and memory precursor effector cells. p38αfl/flp38βfl/flGzmBcre/- … Read more

J Immunol. 2025 Oct 10:vkaf272. doi: 10.1093/jimmun/vkaf272. Online ahead of print. ABSTRACT Sepsis followed by multiple organ failure is a leading cause of death in noncoronary intensive care units. While the NLRC4 inflammasome has been shown to play a crucial role in the innate immune response, the role of NLRC4 in sepsis remains unclear. Here, … Read more

J Immunol. 2025 Oct 8:vkaf123. doi: 10.1093/jimmun/vkaf123. Online ahead of print. ABSTRACT Vaccination strategies and correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly focused on the spike (S) protein and neutralizing antibodies. However, the rapid emergence of SARS-CoV-2 variants has reduced the effectiveness of spike-based vaccines and monoclonal antibodies. It … Read more

J Immunol. 2025 Oct 8:vkaf154. doi: 10.1093/jimmun/vkaf154. Online ahead of print. ABSTRACT Spring viremia of carp virus (SVCV) represents a significant threat to cyprinids, particularly common carp (Cyprinus carpio). The disease caused by this virus is characterized by tissue necrosis and petechial hemorrhages. However, the pathogenesis of SVCV infection remains poorly understood. Pyroptosis, a recently … Read more

J Immunol. 2025 Oct 6:vkaf269. doi: 10.1093/jimmun/vkaf269. Online ahead of print. ABSTRACT Pneumocystis jirovecii pneumonia remains a significant cause of mortality and morbidity in immunocompromised populations worldwide. Mortality rates range from 5% to 30% in HIV-positive individuals and 4% to 76% in those without HIV. Recognizing its public health impact, the World Health Organization (WHO) … Read more

J Immunol. 2025 Oct 3:vkaf224. doi: 10.1093/jimmun/vkaf224. Online ahead of print. ABSTRACT Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of head and neck cancers. HNSCC development is linked to chronic inflammation, while established HNSCC tumors are often immune suppressive. However, both occur through mechanisms that are not fully understood. The cytosolic double-stranded DNA … Read more

J Immunol. 2025 Oct 3:vkaf233. doi: 10.1093/jimmun/vkaf233. Online ahead of print. ABSTRACT Fibroblasts participate in inflammatory responses and play a critical role in the switch from acute to persistent inflammation. Whether fibroblast responses are modulated by signals from their microenvironment is not well established. Insulin signaling and insulin resistance modulate responsiveness of innate immune cells … Read more

J Immunol. 2025 Oct 1:vkaf223. doi: 10.1093/jimmun/vkaf223. Online ahead of print. ABSTRACT Systemic lupus erythematosus is characterized by activation of many self-reactive B cell clones that produce autoantibodies. This can be modeled using mixed bone marrow chimeras, where autoreactive 564Igi B cells initiate autoimmunity that spreads to wild-type (WT) B cells. The mechanisms controlling the … Read more

J Immunol. 2025 Sep 1;214(9):2135-2137. doi: 10.1093/jimmun/vkaf178. NO ABSTRACT PMID:41024741 | DOI:10.1093/jimmun/vkaf178

J Immunol. 2025 Sep 30:vkaf266. doi: 10.1093/jimmun/vkaf266. Online ahead of print. ABSTRACT Mucosa-associated invariant T (MAIT) cells are innate-like T cells abundant in mucosal tissues, liver, and blood. MAIT cells recognize riboflavin metabolite-derived microbial antigens displayed by the MHC-I-related protein (MR1) and respond by producing cytokines, killing infected cells, and suppressing microbial growth. We previously … Read more

J Immunol. 2025 Sep 29:vkaf228. doi: 10.1093/jimmun/vkaf228. Online ahead of print. ABSTRACT Hepatocellular carcinoma (HCC) stands as one of the most prevalent and fatal malignancies globally, posing a persistent challenge in its treatment due to immune evasion. We knocked down MEF2D in HCC cell lines and analyzed HCC tissues and cell lines by RNA sequencing, … Read more

J Immunol. 2025 Sep 27:vkaf240. doi: 10.1093/jimmun/vkaf240. Online ahead of print. ABSTRACT Matrix metalloproteinase 9 (MMP-9) plays a key role in the pathogenesis of inflammatory diseases and is upregulated by TNF-α. ITE (2-[1’H-indole-3′-carbonyl]-thiazole-4-carboxylic acid methyl ester) functions as an endogenous ligand for the aryl hydrocarbon receptor and is involved in inflammation. It is still uncertain … Read more

J Immunol. 2025 Sep 27:vkaf254. doi: 10.1093/jimmun/vkaf254. Online ahead of print. ABSTRACT Foxp3+ regulatory T (Treg) cells with antigen receptors (TCRs) specific for host peptides suppress autoimmunity. Paradoxically, Treg cells are also found in CD4+ T-cell populations specific for foreign (nonhost) peptides. We investigated the origin and function of these Treg cells in mice. Populations … Read more

J Immunol. 2025 Sep 26:vkaf252. doi: 10.1093/jimmun/vkaf252. Online ahead of print. ABSTRACT Tuberculosis (TB), a significant global health issue, needs novel therapeutic approaches to reduce its burden. Studying host-pathogen interactions provides new targets for host-directed therapeutics (HDTs). Nuclear receptors (NRs) are important master regulators of cellular function and bona fide drug targets. Herein, we identify … Read more

J Immunol. 2025 Sep 26:vkaf259. doi: 10.1093/jimmun/vkaf259. Online ahead of print. ABSTRACT Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive immunotherapy potentially applicable to many types of solid tumors. Although gynecologic malignancies are promising targets for TIL therapy, its objective efficacy has not been established. Current TIL culture typically involves incubation of dissociated samples … Read more

J Immunol. 2025 Sep 25:vkaf212. doi: 10.1093/jimmun/vkaf212. Online ahead of print. ABSTRACT Rhesus macaques (RMs) are widely employed as a preclinical model in vaccination and infectious disease studies, yet their B cell immunobiology and immunogenetics remain ill-characterized. In this study, single-cell RNA/VDJ sequencing was conducted on peripheral blood mononuclear cell samples from 6 RMs to … Read more

J Immunol. 2025 Sep 25:vkaf237. doi: 10.1093/jimmun/vkaf237. Online ahead of print. ABSTRACT The rising emergence of antimicrobial-resistant Pseudomonas aeruginosa strains necessitates effective therapeutic strategies like antibody-based immunotherapy. Flagellin is crucial in P. aeruginosa infection development. This study evaluated the antibacterial efficacy of bivalent immunoglobulin Y (IgY) raised against both A and B flagellins. IgY’s immunoreactivity … Read more

J Immunol. 2025 Sep 24:vkaf251. doi: 10.1093/jimmun/vkaf251. Online ahead of print. ABSTRACT Graft failure (GF) following hematopoietic stem cell transplantation (HSCT) remains a major complication particularly in the setting of human leukocyte antigen (HLA)-mismatched grafts where residual host lymphocytes can drive immune-mediated rejection. While strategies to mitigate GF have been explored, such as intensified conditioning … Read more

J Immunol. 2025 Sep 22:vkaf247. doi: 10.1093/jimmun/vkaf247. Online ahead of print. ABSTRACT Obexelimab is an investigational, bifunctional humanized monoclonal antibody that inhibits B-lineage cells by binding CD19 via its Fab region and simultaneously co-engaging the inhibitory receptor FcγRIIb through a modified Fc region. Interactions between B cells and T cells specific for the same Ag … Read more

J Immunol. 2025 Sep 22:vkaf261. doi: 10.1093/jimmun/vkaf261. Online ahead of print. NO ABSTRACT PMID:40981764 | DOI:10.1093/jimmun/vkaf261

J Immunol. 2025 Sep 22:vkaf196. doi: 10.1093/jimmun/vkaf196. Online ahead of print. ABSTRACT In response to an infection, the host T cell compartment develops immunological memory to ensure rapid responses upon re-infection with the same pathogen. However, these memory responses can also modulate immune reactions to unrelated pathogens through bystander activation. Herein, T cells are activated … Read more

J Immunol. 2025 Sep 22:vkaf257. doi: 10.1093/jimmun/vkaf257. Online ahead of print. ABSTRACT Chronic inflammatory diseases are becoming more prevalent in Western countries, yet there is limited research on clinical tools for their cure. Understanding the bacteria in the gastrointestinal tract is crucial for managing these diseases, as pathogenic bacteria can lead to inflammation and cancer, … Read more

J Immunol. 2025 Sep 16:vkaf239. doi: 10.1093/jimmun/vkaf239. Online ahead of print. ABSTRACT The differentiation of CD8 T cells into effector and memory populations is guided by a combination of antigenic, costimulatory, and cytokine signals. Here we show that, within 24 h of activating naïve CD8 T cells, populations emerge with divergent patterns of interleukin (IL)-2 … Read more

J Immunol. 2025 Sep 22:vkaf255. doi: 10.1093/jimmun/vkaf255. Online ahead of print. NO ABSTRACT PMID:40981765 | DOI:10.1093/jimmun/vkaf255

J Immunol. 2025 Sep 16:vkaf245. doi: 10.1093/jimmun/vkaf245. Online ahead of print. ABSTRACT Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immunoglobulin (IVIG) therapy and frequently develop coronary artery lesions (CAL) that result in long-term complications. Transcriptome studies utilizing blood cells from KD patients and … Read more

J Immunol. 2025 Sep 16:vkaf242. doi: 10.1093/jimmun/vkaf242. Online ahead of print. ABSTRACT Tumor-infiltrating lymphocyte (TIL) therapy is a promising approach, earning U.S. Food and Drug Administration approval in patients with anti-PD-1-resistant melanoma. Extending TIL therapy to patients with cholangiocarcinoma (CCA), an aggressive and largely immune-refractory cancer, is an emerging area of interest. However, cost and … Read more

J Immunol. 2025 Sep 16:vkaf243. doi: 10.1093/jimmun/vkaf243. Online ahead of print. ABSTRACT Disruptor of telomeric silencing 1-like (DOT1L) is an epigenetic regulator that promotes gene expression by methylating lysine 79 on histone H3 and recruits transcription factors to gene targets. DOT1L is also an oncogenic driver in cancers that affect developing lymphocytes, yet how DOT1L … Read more

J Immunol. 2025 Sep 16:vkaf197. doi: 10.1093/jimmun/vkaf197. Online ahead of print. ABSTRACT Pulmonary infections often fail to produce long-lived immune memory and the underlying mechanism(s) for this are unclear. Given the complex interactions between cells within the lung, we predicted intrinsic and extrinsic factors contribute to development of poor memory immune responses. To identify these … Read more

J Immunol. 2025 Sep 16:vkaf253. doi: 10.1093/jimmun/vkaf253. Online ahead of print. ABSTRACT The tumor microenvironment (TME) plays a pivotal role in shaping immune responses and therapeutic outcomes in lung cancer, yet the diversity and functional specialization of tumor-associated macrophages (TAMs) remain poorly resolved. Here, we present a refined classification of TAM subtypes across large cohorts … Read more

J Immunol. 2025 Sep 15:vkaf227. doi: 10.1093/jimmun/vkaf227. Online ahead of print. ABSTRACT Although the interplay between the complement system, platelets, and neutrophils has been considered a major contributor to inflammation and thrombogenicity, little attention has been directed toward understanding their roles in people living with human immunodeficiency virus (PLWH). We quantified and compared expression levels … Read more

J Immunol. 2025 Sep 15:vkaf246. doi: 10.1093/jimmun/vkaf246. Online ahead of print. ABSTRACT Blood coagulation and immune responses have long been considered as discrete processes. However, recent studies have revealed that mammalian platelets play a critical role in immune regulation in addition to their well-established role in hemostasis. This dual functionality suggests an evolutionary link between … Read more

J Immunol. 2025 Sep 15:vkaf200. doi: 10.1093/jimmun/vkaf200. Online ahead of print. ABSTRACT The intestinal mucosa in individuals with chronic human immunodeficiency virus (HIV) infection remains a site of viral persistence and immune dysregulation, even with prolonged suppressive antiretroviral therapy (ART). While biomarkers of mucosal damage and microbial translocation offer valuable correlative insights, the underlying mechanisms … Read more

J Immunol. 2025 Sep 15:vkaf213. doi: 10.1093/jimmun/vkaf213. Online ahead of print. ABSTRACT Osteoarthritis (OA) is characterized by cartilage destruction and immune cell infiltration, of which include myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to expand in obese patients with OA. Therefore, we aimed to investigate the role of obesity on MDSC function in knee … Read more

J Immunol. 2025 Sep 13:vkaf241. doi: 10.1093/jimmun/vkaf241. Online ahead of print. NO ABSTRACT PMID:40971647 | DOI:10.1093/jimmun/vkaf241

J Immunol. 2025 Sep 16:vkaf248. doi: 10.1093/jimmun/vkaf248. Online ahead of print. ABSTRACT Natural killer (NK) cells are pivotal innate lymphoid cells in anti-tumor immunity. However, the contribution of the Y chromosome-encoded epigenetic regulator UTY (also known as KDM6C) to male NK cell development and effector function remains poorly characterized. Here, we demonstrated that conditional deletion … Read more

J Immunol. 2025 Sep 9:vkaf229. doi: 10.1093/jimmun/vkaf229. Online ahead of print. ABSTRACT Hepatitis B virus (HBV) exclusively infects hepatocytes and produces large quantities of subviral particles containing its surface antigen (HBsAg). T cells play a central role in controlling HBV infection but can also mediate liver injury and contribute to disease progression. However, the mechanisms … Read more

J Immunol. 2025 Sep 4:vkaf215. doi: 10.1093/jimmun/vkaf215. Online ahead of print. ABSTRACT Mounting evidence supports a critical role for central nervous system (CNS) glial cells in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), as well as neurovascular ischemic stroke. Previously, we found that loss of the PD-associated gene … Read more

J Immunol. 2025 Sep 4:vkaf219. doi: 10.1093/jimmun/vkaf219. Online ahead of print. ABSTRACT Tissue resident memory T cells (TRM) provide protection against local re-infection, and yet the interstitial signals that govern their formation and persistence remain poorly defined. Here, we show that antigen-dependent induction of the chemokine receptor CXCR6, is a conserved adaptation to peripheral tissue … Read more

J Immunol. 2025 Sep 3:vkaf226. doi: 10.1093/jimmun/vkaf226. Online ahead of print. ABSTRACT Mucosal-associated invariant T (MAIT) cells play a vital role in immune responses, yet their involvement in autoimmune diseases such as Sjögren’s disease (SjD) remains unclear. CD55, a key regulator of complement activation, influences immune cell function. This study investigates CD55 expression on MAIT … Read more

J Immunol. 2025 Sep 3:vkaf216. doi: 10.1093/jimmun/vkaf216. Online ahead of print. ABSTRACT Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine that is overexpressed in tumor microenvironments. We have shown that CD8+ T cells with genetic ablation of the TGFβ type I receptor, Alk5 (CD8ΔALK5), were more sensitive to αCD3 stimulation resulting in enhanced proliferation … Read more

J Immunol. 2025 Sep 3:vkaf220. doi: 10.1093/jimmun/vkaf220. Online ahead of print. ABSTRACT The Feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) pathway is associated with pathogenesis of several autoimmune diseases, including Sjögren’s. Inflammatory signals increase FLT3L levels; FLT3L signaling promotes further inflammation through the differentiation, function, and survival of immune cells, including dendritic cells … Read more

J Immunol. 2025 Sep 2:vkaf206. doi: 10.1093/jimmun/vkaf206. Online ahead of print. ABSTRACT Adjuvants are widely used to boost the immune response during vaccination protocols. Our group has previously reported that repeated intraperitoneal administration of alum in mice, known as adjuvant conditioning (AC), creates an immunosuppressive environment that delays allogeneic graft rejection through NLRP3-dependent MDSC expansion. … Read more

J Immunol. 2025 Sep 1:vkaf230. doi: 10.1093/jimmun/vkaf230. Online ahead of print. ABSTRACT The γδ TCR instructively directs both lineage specification and effector programming of developing γδ T cells. However, the way in which different TCR signal strengths and other auxiliary signals coordinate downstream of the γδ TCR to regulate γδ T-cell development remains unclear. In … Read more

J Immunol. 2025 Aug 29:vkaf210. doi: 10.1093/jimmun/vkaf210. Online ahead of print. ABSTRACT Persistent antigen exposure during chronic viral infection and tumor development drives CD8 T cells into an exhausted, hypofunctional state. Understanding the molecular pathways that enforce T-cell exhaustion is critical for improving current immunotherapies. Previously, we have shown the bioactive lipid lysophosphatidic acid (LPA) … Read more

J Immunol. 2025 Aug 1;214(8):1861-1862. doi: 10.1093/jimmun/vkaf175. NO ABSTRACT PMID:40878575 | DOI:10.1093/jimmun/vkaf175

J Immunol. 2025 Aug 1;214(8):1881-1888. doi: 10.1093/jimmun/vkaf128. ABSTRACT Programmed cell death is an integral arm of immunity, especially in response to intracellular pathogen infection, for the release of inflammatory mediators, and the clearance of pathogen-infected cells. In the central nervous system, cell death as a form of immunity may seem paradoxical; neuronal health is critical … Read more

J Immunol. 2025 Aug 1;214(8):1863-1871. doi: 10.1093/jimmun/vkaf116. ABSTRACT The lymphatics are a system of vessels that traffic lymph and immune cells throughout the body to maintain fluid balance and aid in the response to infection and injury. Although the lymphatics are often thought of as a passive conduit, this review will demonstrate that the lymphatics … Read more

J Immunol. 2025 Aug 28:vkaf208. doi: 10.1093/jimmun/vkaf208. Online ahead of print. ABSTRACT The main limitations of cancer treatment with high doses of recombinant interleukin 2 (IL-2) are high toxicity and the undesired expansion of regulatory T cells. The generation of IL-2 mutated variants (muteins) with changes in the affinity for different chains of the IL-2 … Read more

J Immunol. 2025 Aug 28:vkaf177. doi: 10.1093/jimmun/vkaf177. Online ahead of print. ABSTRACT Identifying cell intrinsic regulators of immune sexual dimorphism is critical for treatment of several immunopathologies. We show that Malat1 is required for appropriate cytokine expression in female but not male T helper 2 (Th2) cells. Malat1 deficiency impairs in vitro Th2 differentiation of … Read more

J Immunol. 2025 Aug 25:vkaf194. doi: 10.1093/jimmun/vkaf194. Online ahead of print. ABSTRACT As a result of the growing use of nuclear energy and radiation in medical interventions within the last decade, the potential for radiation exposure among the general public has increased. Exposure to high doses of radiation severely impairs the immune system, including CD8 … Read more

J Immunol. 2025 Aug 25:vkaf209. doi: 10.1093/jimmun/vkaf209. Online ahead of print. ABSTRACT Natural killer (NK) cells are innate immune lymphocytes important for host viral and tumor immunity. We investigated the requirement for ATP citrate lyase (ACLY) in NK cell function using an inducible genetic mouse model. ACLY regulates the citrate-malate shuttle, generating cytosolic acetyl-coenzyme A … Read more

J Immunol. 2025 Aug 24:vkaf187. doi: 10.1093/jimmun/vkaf187. Online ahead of print. ABSTRACT CD39 (encoded by ENTPD1) has emerged as a target for oncologic therapies. Inhibition of CD39 preserves extracellular adenosine triphosphate (eATP) and decreases extracellular adenosine (eADO) formation, thereby increasing the eATP/eADO ratio and promoting immune stimulation. RNA expression profiling of eATPases across all solid … Read more

J Immunol. 2025 Aug 24:vkaf211. doi: 10.1093/jimmun/vkaf211. Online ahead of print. ABSTRACT Sjögren syndrome-related interstitial lung disease (SS-ILD) is a severe complication associated with significant morbidity and mortality. Despite its clinical importance, the underlying pathogenesis remains poorly understood, and effective therapeutic strategies are limited. The development of a reliable animal model for SS-ILD is crucial … Read more

J Immunol. 2025 Aug 24:vkaf199. doi: 10.1093/jimmun/vkaf199. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has proven to be a promising treatment for multiple types of cancer. Yet, the mechanisms regulating CAR T-cell function as well as the side effects remain an area of active research. The formation of the immunological synapse … Read more

J Immunol. 2025 Aug 24:vkaf207. doi: 10.1093/jimmun/vkaf207. Online ahead of print. ABSTRACT Allergic rhinitis (AR) is a respiratory airway disorder characterized by inflammation and barrier dysfunction. The transcription factor specificity protein 1 (SP1), a member of the Sp/Krüppel-like factor family, is known to be associated with inflammation. This study aimed to explore the impacts of … Read more

J Immunol. 2025 Aug 24:vkaf217. doi: 10.1093/jimmun/vkaf217. Online ahead of print. ABSTRACT V(D)J recombination is constrained by timely degradation of the RAG1 and RAG2 proteins through distinct mechanisms. Previously, we showed that full-length RAG1 stability is regulated by viral protein R binding protein (VprBP) through its association with an amino-terminal region in RAG1, but the … Read more

J Immunol. 2025 Aug 24:vkaf205. doi: 10.1093/jimmun/vkaf205. Online ahead of print. ABSTRACT While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecule’s distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56+CD20+ NK … Read more

J Immunol. 2025 Aug 22:vkaf180. doi: 10.1093/jimmun/vkaf180. Online ahead of print. ABSTRACT The pathomechanistic role of the complement system is well recognized in various pathological conditions affecting bone tissues and the bone microenvironment, including rheumatoid arthritis, osteoarthritis, bone fractures, and periodontitis. The homeostasis of the bone is maintained by continuous remodeling, in which bone-resorbing or … Read more

J Immunol. 2025 Aug 22:vkaf165. doi: 10.1093/jimmun/vkaf165. Online ahead of print. ABSTRACT CD8 T cell exhaustion has been reported in mice susceptible to Toxoplasma gondii infection. While the differentiation of CD8 exhausted subsets has been extensively reported, most of these studies have been conducted in chronic viral and cancer models. During chronic T. gondii infection, … Read more

J Immunol. 2025 Aug 22:vkaf195. doi: 10.1093/jimmun/vkaf195. Online ahead of print. ABSTRACT Lyme disease (LD) is the most common vector-borne disease in the northern hemisphere and is caused by the bacteria Borrelia burgdorferi sensu lato (also known as Lyme borreliae) with no effective prevention available. Lyme borreliae evade complement killing, a critical arm of host … Read more

J Immunol. 2025 Aug 21:vkaf183. doi: 10.1093/jimmun/vkaf183. Online ahead of print. ABSTRACT Accurate identification of immune cell subsets in single-cell RNA sequencing (scRNA-seq) data is critical for understanding immune responses in autoimmune diseases, infections, and cancer. One caveat of scRNA-seq is the inability to properly assign rare immune cell subsets due to gene dropout events. … Read more

J Immunol. 2025 Aug 20:vkaf179. doi: 10.1093/jimmun/vkaf179. Online ahead of print. ABSTRACT Bcl11b is a zinc-finger transcription factor that is required for the differentiation of αβ T cells. A role for BCL11B in the regulation of human natural killer (NK) cell maturation has been inferred from patients with heterozygous mutations in BCL11B. However, mechanistic and … Read more

J Immunol. 2025 Aug 20:vkaf201. doi: 10.1093/jimmun/vkaf201. Online ahead of print. ABSTRACT C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and … Read more

J Immunol. 2025 Aug 19:vkaf192. doi: 10.1093/jimmun/vkaf192. Online ahead of print. ABSTRACT Toll-like receptor 4 (TLR4), a critical pattern recognition receptor, detects microbe- and damage/danger-associated molecular patterns to trigger immune responses in mammals. However, the functions and mechanisms remain largely unclear in lower vertebrates. This study systematically investigates the evolutionary divergence, subcellular localization and ligand … Read more

J Immunol. 2025 Aug 18:vkaf202. doi: 10.1093/jimmun/vkaf202. Online ahead of print. ABSTRACT Macrophages comprise the first line of host responses against injury and pathogens and therefore are critically engaged in tissue repair, host defense, and homeostasis maintenance. Depending on the surrounding microenvironment, macrophages polarize into a wide spectrum of immunophenotypes with 2 extreme opposite ends-proinflammatory … Read more

J Immunol. 2025 Aug 18:vkaf204. doi: 10.1093/jimmun/vkaf204. Online ahead of print. ABSTRACT NOD2 is primarily recognized as a cytosolic bacterial sensor of peptidoglycan, activating a downstream Rip2/NF-κB-mediated antimicrobial signaling pathway and playing a vital role in host defense against bacterial infections. NOD2 also appears to play a critical role in immune homeostasis, as NOD2 variants … Read more

J Immunol. 2025 Aug 18:vkaf193. doi: 10.1093/jimmun/vkaf193. Online ahead of print. ABSTRACT The thymus is a primary lymphoid organ generating self-restricted and self-tolerant naïve T cells. Early in life the thymus starts to involute, resulting in decreased naïve T cell output which may be more self-reactive, leading to an increased prevalence of autoimmunity. A decrease … Read more

J Immunol. 2025 Aug 14:vkaf198. doi: 10.1093/jimmun/vkaf198. Online ahead of print. ABSTRACT Brucella abortus exploits the endoplasmic reticulum as a site for replication, triggering the unfolded protein response (UPR). While various pathogens have developed strategies to manipulate mitochondrial dynamics, the mechanisms underlying bacterial infection and mitochondrial dynamics interactions remain poorly understood. Here, we demonstrate that … Read more

J Immunol. 2025 Aug 13:vkaf203. doi: 10.1093/jimmun/vkaf203. Online ahead of print. ABSTRACT The transcriptional regulatory elements and epigenetic modifiers predominantly control the molecular pathways influencing the development of the immune system. Recently, microRNAs (miRNAs) have emerged as a new class of immune system regulators, playing an indispensable role in the ontogenesis, differentiation, activation, and function … Read more

J Immunol. 2025 Aug 13:vkaf185. doi: 10.1093/jimmun/vkaf185. Online ahead of print. ABSTRACT Humanized (h) DRAGA mice are a promising in vivo model for investigating immunotherapies for treating HIV infections. These mice are not only susceptible to HIV infection, but they also develop functional human immune cells, including T cells and B cells, as well as … Read more

J Immunol. 2025 Aug 12:vkaf182. doi: 10.1093/jimmun/vkaf182. Online ahead of print. ABSTRACT Immune checkpoint blockade has been shown to restore anti-tumor T-cell function and elicit durable responses in select solid and hematopoietic malignancies. However, single-agent anti-programmed death 1 (PD-1) antibodies proved less efficacious in patients with chronic lymphocytic leukemia (CLL). In patients with high-risk or … Read more

J Immunol. 2025 Aug 12:vkaf189. doi: 10.1093/jimmun/vkaf189. Online ahead of print. ABSTRACT It was previously reported that genetic ablation of the NF-κB atypical inhibitor Bcl3 through congenic introduction of a 129P2-embryo derived knockout allele (Bcl3tm1Ver) accelerated autoimmune diabetes in the NOD mouse model. Conversely, we found that direct CRISPR-mediated ablation of this gene in the … Read more

J Immunol. 2025 Aug 12:vkaf167. doi: 10.1093/jimmun/vkaf167. Online ahead of print. ABSTRACT Since its approval in 2019, hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, like roxadustat, have been used for treatment of anemia in chronic kidney disease. However, the impact of HIF stabilization on circulating leukocytes remains largely unexplored. In this study, we examined how clinically … Read more

J Immunol. 2025 Aug 7:vkaf174. doi: 10.1093/jimmun/vkaf174. Online ahead of print. ABSTRACT Natural killer (NK) cells are specialized lymphocytes that help protect against viruses and cancer. However, in the context of bacterial infections, NK cells can be harmful, rather than protective. Such immune pathogenesis by NK cells has been linked to the overproduction of proinflammatory … Read more

J Immunol. 2025 Aug 7:vkaf164. doi: 10.1093/jimmun/vkaf164. Online ahead of print. ABSTRACT Although alternatively-activated macrophages (AAM) have been implicated in the resolution of inflammation and tissue repair, their exact role, heterogeneity and origin in vivo remain incompletely defined. Here we show that distinct subsets of macrophages can acquire alternatively activated phenotypes in response to tissue … Read more

J Immunol. 2025 Aug 8:vkaf186. doi: 10.1093/jimmun/vkaf186. Online ahead of print. ABSTRACT Tuberculous meningitis (TBM) is the most severe form of tuberculosis, with a fatality rate of 20% to 50% in treated individuals. Although corticosteroid therapy can increase survival in HIV-negative people with TBM, better antimicrobial and host-directed therapies are required to improve outcome. There … Read more

J Immunol. 2025 Aug 8:vkaf191. doi: 10.1093/jimmun/vkaf191. Online ahead of print. ABSTRACT Legionella pneumophila causes severe pneumonia, resulting in acute lung injury. L. pneumophila pneumonia induces neutrophil recruitment to the lung through CXC chemokines. Previously, blocking CXCR2, the common receptor for CXC chemokines, but not CXCL1 or CXCL2, resulted in attenuated neutrophil accumulation and reduced … Read more

J Immunol. 2025 Aug 7:vkaf155. doi: 10.1093/jimmun/vkaf155. Online ahead of print. ABSTRACT Tumor clearance by T cells is impaired by insufficient tumor antigen recognition, insufficient tumor infiltration, and the immunosuppressive tumor microenvironment. Although targeted T cell therapy circumvents failures in tumor antigen recognition, suppression by the tumor microenvironment and failure to infiltrate the tumor can … Read more

J Immunol. 2025 Aug 7:vkaf156. doi: 10.1093/jimmun/vkaf156. Online ahead of print. ABSTRACT Diet-induced obesity leads to dysregulated myelopoiesis and nonresolving inflammation. Such dysregulation could involve epigenetic reprogramming, which can induce long-term changes in hematopoietic stem and progenitor cells (HSPCs). However, whether and how obesity-dysregulated HSPCs impact myelopoiesis in response to tissue injury are not fully … Read more

J Immunol. 2025 Aug 7:vkaf190. doi: 10.1093/jimmun/vkaf190. Online ahead of print. ABSTRACT Immunoglobulin GM (γ marker) allotypes are encoded by 3 very closely linked and highly homologous immunoglobulin heavy chain G (IGHG) genes-IGHG1, IGHG2, and IGHG3-on chromosome 14q32. They are localized on the constant region of γ1, γ2, and γ3 chains. There are currently 18 … Read more

J Immunol. 2025 Aug 7:vkaf160. doi: 10.1093/jimmun/vkaf160. Online ahead of print. ABSTRACT The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 … Read more

J Immunol. 2025 Aug 7:vkaf141. doi: 10.1093/jimmun/vkaf141. Online ahead of print. ABSTRACT Immunity against skin-invasive pathogens requires mechanisms that rapidly detect, repel, or immobilize the infectious agent. While bacteria often cause painful cutaneous reactions, host skin invasion by the human parasitic helminth Schistosoma mansoni often goes unnoticed. This study interrogated whether pain-sensing skin afferents marked … Read more

J Immunol. 2025 Aug 7:vkaf184. doi: 10.1093/jimmun/vkaf184. Online ahead of print. ABSTRACT Human macrophages differ from their mouse counterparts in multiple metabolic pathways, surface protein expression, and transcription factor biology. Monocyte-derived macrophages (MDMs) from blood are generally used to study human macrophage biology in vitro. However, the use of MDMs as a human macrophage model … Read more

J Immunol. 2025 Aug 1:vkaf094. doi: 10.1093/jimmun/vkaf094. Online ahead of print. ABSTRACT T cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR variable regions was generated in the previous century. … Read more

J Immunol. 2025 Aug 1:vkaf112. doi: 10.1093/jimmun/vkaf112. Online ahead of print. ABSTRACT Total joint arthroplasty is the optimal method for end-stage osteoarticular diseases, but aseptic loosening reduces long-term success. Our prior research demonstrated that wear particles released from loosened prostheses activate macrophages to secrete proinflammatory cytokines, thereby promoting osteoclast formation and osteolysis. Gasdermin D (GSDMD), … Read more