Immunology最新文献

{"title":"Signal Transducer and Activator of Transcription (STAT) Proteins Regulate Mucosal-Associated Invariant T (MAIT) Cell Function.","authors":"Olivia J Cheng, Eimear K Ryan, Michael Bennett, Christy Clutter, Jackson G Cacioppo, Jeffrey Aubé, Andy E Hogan, Daniel T Leung","doi":"10.1111/imm.70086","DOIUrl":"10.1111/imm.70086","url":null,"abstract":"<p><p>Mucosal-Associated Invariant T (MAIT) cells are a subset of T cells with potential for rapid cytotoxic and inflammatory functions. Dysregulation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway, particularly involving STAT1 and STAT3, has been implicated in MAIT cell dysfunction in certain diseases. However, the transcriptional mechanisms regulating their effector functions, particularly the role of various STAT proteins, remain poorly understood. Using RNA sequencing and proteomics data, and experimental validation through in vitro assays using MAIT-specific stimulation and small molecule inhibitors, we analysed the impact of STAT1, STAT3 and STAT5 on MAIT cell activation and function. Flow cytometric analysis was used to assess the functional implications of manipulating STAT proteins and the metabolic regulator HIF1α in MAIT cells. Our findings show that enhanced STAT1 activity negatively impacts MAIT cell effector functions, including granzyme B and interferon-γ expression, while STAT3 and STAT5 are essential for promoting MAIT cell activation, function and glycolytic responses. Additionally, we identify HIF1α as a key regulator of these processes, suggesting that metabolic reprogramming plays a critical role in MAIT cell activation and function. This study highlights the critical roles of STAT1, STAT3, STAT5 and HIF1α in regulating MAIT cell effector functions, expanding our understanding of the molecular mechanisms underlying MAIT cell dysfunction. Our work lays the foundation for future research and applications aimed at modulating MAIT cell activity in immune-related diseases and malignancies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"97-108"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Response to Vunakizumab at Week 2 Predicts Favourable Long-Term Efficacy in Patients With Moderate-To-Severe Plaque Psoriasis: A Post Hoc Analysis of a Phase III, Randomised Controlled Trial.","authors":"Xiaoying Sun, Yaohua Zhang, Xiya Lu, Suwei Tang, Fujuan Chen, Ziwen Sun, Xin Li","doi":"10.1111/imm.70099","DOIUrl":"10.1111/imm.70099","url":null,"abstract":"<p><p>This study was a post hoc analysis of a Phase III trial (NCT04839016), which aims to investigate whether early response to vunakizumab can predict long-term efficacy in plaque psoriasis patients. A total of 461 plaque psoriasis patients receiving vunakizumab treatment were included for analysis. Early response to vunakizumab was defined by patients achieving a psoriasis area and severity index (PASI) 50 at week (W) 2. Efficacy analysis included PASI 75/90/100 and static physician's global assessment (sPGA) 0/1 response rates in both groups. Safety was analysed in both groups. At W2, 249 patients achieved an early response; 212 did not. At W12, higher proportions of patients in the early response group achieved PASI 75/90/100 and sPGA 0/1 versus the without early response group (98.4% vs. 88.2%, 88.0% vs. 66.0%, 50.2% vs. 25.0%, 84.7% vs. 64.6%, respectively; all p < 0.001). The early response group had higher proportions of patients who maintained PASI 75/90/100 and sPGA 0/1 from W12 to W52 versus the without early response group (88.8% vs. 76.4%, 74.7% vs. 54.7%, 39.4% vs. 20.8%, 68.7% vs. 54.2%, respectively; all p < 0.001). Multivariate logistic regression analysis showed that early response to vunakizumab was independently associated with PASI 100 response at W52 (odds ratio = 1.772, p = 0.027). The incidence of adverse events was similar between groups. Patients with moderate-to-severe plaque psoriasis receiving vunakizumab show a favourable clinical response, regardless of achieving early response or not. Particularly, patients with early response at Week 2 are significantly more likely to achieve better long-term treatment outcomes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"162-173"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysfunctional Dendritic Cells in Radiation-Induced Jaw Injury: Insights From Single-Cell Transcriptomic Analysis of the Osteoimmune Microenvironment.","authors":"Mengting Zheng, Heng Chen, Zhonglong Liu, Xiaoyan Meng, Ting Jiang, Mengyu Li, Yue He","doi":"10.1111/imm.70088","DOIUrl":"10.1111/imm.70088","url":null,"abstract":"<p><p>Radiation-induced jaw injury is a serious and debilitating complication following head and neck radiotherapy (RT). The irradiation process triggers the recruitment and maladaptive activation of immune cells, thereby disrupting the delicate homeostasis of the jawbone. Despite its clinical significance, a comprehensive understanding of the osteoimmune microenvironment involved in underlying radiation-induced jaw injury remains incompletely understood. In this study, we comprehensively profiled the transcriptional landscape of mandibular bone marrow at single-cell resolution using single-cell RNA sequencing (scRNA-seq). Our analysis revealed a marked infiltration of conventional dendritic cells (cDCs). A specific subcluster of migratory dendritic cells (migDCs) characterised by the expression of genes related to maturation, migration and immune regulation was annotated. Following RT, these migDCs migrated to the draining lymph nodes. However, reduced secretion of neutrophil-derived secreted phosphoprotein 1 (SPP1) was found to impair migDC development through the SPP1/CD44/NF-κB signalling pathway, leading to an immature cDC phenotype. We also observed weakened intercellular interactions between cDCs and T cells, contributing to an imbalanced and immunosuppressive osteoimmune microenvironment after radiation exposure. Overall, our study highlights the critical role of decreased SPP1 in modulating migDC function and its subsequent impact on jawbone immune dynamics following RT.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"118-135"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Pathway for Intercepting Granular Exocytosis: A13 Engages APLNR to Drive FBXO28-Mediated Ubiquitination and Proteasomal Clearance of Rab27a in Allergic Inflammation.","authors":"Gaohui Wu, Yanyu Ye, Jiaqi Duan, Minyao Li, Yun Liao, Pingchang Yang, Qinmiao Huang, Yu Liu","doi":"10.1111/imm.70135","DOIUrl":"https://doi.org/10.1111/imm.70135","url":null,"abstract":"<p><p>Allergic airway inflammation (AA) is primarily driven by the activation of mast cells and eosinophils, with granular exocytosis serving as a key source of pro-allergic mediators that amplify pathological responses. This unmet need highlights the importance of identifying novel, pathway-specific therapeutic targets to improve disease management. A dust mite extract (DME)-induced murine model of AA was used to assess intranasal A13 (1 mg/kg daily) efficacy; human EoL-1 eosinophils and murine P815 mast cells were stimulated with PMA/ionomycin (P&I) to induce exocytosis. In DME-induced murine AA, intranasal A13 reduced lung inflammation by 58% (p < 0.01), serum sIgE by 73% (p < 0.001), and BALF Th2 cytokines (IL-4/IL-5/IL-13) by 65%-80% (p < 0.001), while restoring BALF IFN-γ (p < 0.01). A13 inhibited granular mediator release: in P&I-challenged WT mice, it reduced BALF eosinophil peroxidase (EPX) by 81% and mast cell protease-1 by 85%, but had no effect in APLNR⁻^/⁻ mice (p > 0.05). Mechanistically, P&I induced Rab27a upregulation (P815: 3.2-fold; EoL-1: 2.8-fold), which A13 reversed in vitro; in vivo, A13 lowered lung granulocyte Rab27a by 2.5-3.1-fold (p < 0.001). A13 engaged APLNR to recruit FBXO28, promoting K48-linked Rab27a ubiquitination and proteasomal degradation. APLNR knockdown or MG132 treatment abrogated A13's effects, while A13 enhanced FBXO28-Rab27a complex formation by 4.7-fold (p < 0.001)-an interaction undetectable in APLNR^-/- cells. Intranasal A13 exhibits localised action, effectively suppressing allergic inflammation without broad systemic immunosuppression, making it a promising candidate for development as a topical biologic to treat allergic airway diseases.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD49f Expression in CD4+ T Cells and CD4 + FoxP3+ Tregs Reveals Immune Dysregulation and Potential Diagnostic Value in Systemic Lupus Erythematosus.","authors":"Xiaoning Chen, Weijie Lin, Bing Shen, Ziqi Xiong, Zhiwei Zong, Jie Chen, Bohao Yang, Hanxi Luo, Ayibaota Bahabayi, Chen Liu","doi":"10.1111/imm.70106","DOIUrl":"10.1111/imm.70106","url":null,"abstract":"<p><p>This study aimed to characterise the expression and functional heterogeneity of CD49f across CD4+ T cell subsets in human peripheral blood, and to investigate alterations in regulatory T cells (Tregs) and CD4+ T cells in patients with systemic lupus erythematosus (SLE), together with their clinical relevance. A total of 43 newly diagnosed, treatment-naïve SLE patients and 21 age- and sex-matched healthy controls were enrolled. Peripheral blood mononuclear cells were analysed by flow cytometry to assess CD49f expression in CD4 + FoxP3+ Tregs and non-Treg CD4+ T cells. Phenotypic and function-related markers were compared between CD49f + and CD49f- subsets. IL-10 production was evaluated as a functional readout in CD49f-defined Treg subsets. Associations between CD49f-related populations and clinical parameters were analysed, and receiver operating characteristic (ROC) curve analysis was performed to explore their potential clinical relevance. CD49f expression was higher in CD4 + FoxP3+ Tregs than in other CD4+ T cells. CD49f + CD4+ T cells exhibited increased CD226 and decreased CD45RA expression, consistent with an activated phenotype. CD49f + Tregs were enriched in the CD45RA-FoxP3int subset and showed higher CD226 but lower GZMB and Helios expression, indicating attenuated suppressive phenotypic features. In healthy controls, CD49f + Tregs displayed significantly higher IL-10 production than CD49f- Tregs, whereas this functional distinction was lost in SLE patients. The proportions of CD49f + subsets were significantly increased in SLE and correlated with multiple clinical indicators. ROC analysis revealed moderate discriminative performance of CD49f-related subsets, with AUC values ranging from 0.640 to 0.786. In conclusion, CD49f identifies distinct phenotypic and functional states within CD4+ T cells and Tregs. CD49f + CD4+ T cells exhibit activation features, while CD49f + Tregs show phenotypic attenuation accompanied by functional heterogeneity that is preserved in health but disrupted in SLE. Increased CD49f expression in SLE reflects immune imbalance and suggests potential value as a cellular immunological marker rather than a standalone diagnostic tool.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"197-208"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophil Biology Today-A Primer for Basic and Clinical Investigators.","authors":"Bruno Marques Vieira, Pedro Xavier-Elsas, Vivaldo Moura-Neto, Maria Ignez Capella Gaspar-Elsas","doi":"10.1111/imm.70104","DOIUrl":"10.1111/imm.70104","url":null,"abstract":"<p><p>Eosinophils are multifunctional granulocytes that participate in tissue homeostasis, host defence, inflammation, and repair. Their activities are now known to extend beyond type-2 immunity and include the release of diverse cytokines and growth factors, such as IL-4, IL-13, TGF-β, IL-1β, GM-CSF, and TNF-α, together with context-dependent immunomodulatory, cytotoxic, and pro-remodelling functions. Recent advances highlight the importance of tissue imprinting and microenvironmental cues in shaping eosinophil phenotypes, revealing substantial functional plasticity and transcriptional diversity across physiological and pathological settings. Here we synthesise essential concepts in eosinophil biology and provide an overview of the most widely used approaches for visualising, isolating, and functionally characterising these cells, emphasising methodological strengths, limitations, and common artefacts. We further outline how transcriptomic and proteomic tools have refined the understanding of eosinophil phenotypes and their relevance to disease, including allergy, infection, tissue repair, and cancer. Overall, we provide a resource for basic and clinical investigators who are not currently working in eosinophil biology, but might be attracted to this multidisciplinary area in view of many recent exciting developments.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"79-96"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and Strategies to Enhance CAR-T Cell Infiltration in Solid Tumours: A Systematic Review.","authors":"Yan Zhang, Huihui Sun, Lianfeng Zhao, Ningning Zhao, Zhengliang Chen, Lingfeng He, Zhigang Guo, Jun Yu","doi":"10.1111/imm.70094","DOIUrl":"10.1111/imm.70094","url":null,"abstract":"<p><p>Chimeric antigen receptor T (CAR-T) cell therapy has revolutionised the treatment of hematologic malignancies, achieving durable and robust responses. However, the application of CAR-T cells in solid tumours remains limited by a complex network of barriers, most notably poor tumour infiltration. The key obstacles include mismatch between chemokines and receptors, abnormal tumour vasculature, immunosuppressive cellular populations (such as myeloid-derived suppressor cells, tumour-associated macrophages and regulatory T cells), dense network of cancer-associated fibroblasts and extracellular matrix, T cell dysfunction and exhaustion, metabolic limitations within the tumour microenvironment, tumour heterogeneity and transport limitations related to tumour location. By integrating mechanistic insights with innovative bioengineering and combination approaches, this review systematically elaborates on the factors that limit the infiltration of CAR-T cells and emphasises transformation strategies for improving the efficacy, durability and invasiveness of treating solid tumours.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"62-78"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Regulation in the Tumour Microenvironment: The Interaction Between Tumour-Associated Macrophages and T Cells Reshapes the Paradigm of Cancer Immunotherapy.","authors":"Yuting Li, Lufang Wang","doi":"10.1111/imm.70103","DOIUrl":"10.1111/imm.70103","url":null,"abstract":"<p><p>This review provides an in-depth analysis of the complex bidirectional interaction mechanisms between tumour-associated macrophages (TAMs) and T cells in the tumour microenvironment (TME). It elaborates on how TAMs, especially M2-type TAMs, suppress the anti-tumour function of T cells and induce their exhaustion through multiple pathways, such as secreting immunosuppressive cytokines (e.g., IL-10, TGF-β), highly expressing immune checkpoint ligands (e.g., PD-L1), recruiting other immunosuppressive cells (e.g., Treg cells), depleting key metabolites (e.g., arginine), and remodelling the extracellular matrix (ECM), thereby promoting tumour immune escape and disease progression. Meanwhile, the review also explores how T cells reverse-regulate the polarization state of TAMs through the activation of the CD40-CD40L axis and the secretion of specific cytokines (e.g., IFN-γ or IL-4). Based on this, the review systematically proposes innovative immunotherapy strategies targeting this key bidirectional interaction, including blocking the recruitment of TAMs (e.g., CCL2/CCR2, CXCL12/CXCR4 inhibitors), directly eliminating TAMs (e.g., CSF1R inhibitors, bisphosphonates, trabectedin), or reprogramming them into anti-tumour M1-type (e.g., CD40 agonists, TLR agonists, CD47-SIRPα axis blockers), and emphasises the great potential of combining these TAM-targeting strategies with immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies). These combined therapies aim to synergistically enhance efficacy and overcome the current challenges of drug resistance in immunotherapy, offering new hope for more durable and effective treatment for cancer patients. Additionally, the review looks forward to the application prospects of advanced cell therapies such as nanoparticle delivery systems and chimeric antigen receptor macrophages (CAR-M) in reshaping the TME and enhancing anti-tumour immune responses, providing multi-dimensional and in-depth theoretical basis and practical directions for future cancer immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"1-22"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paediatric Solid Tumour Vaccines: Current Processes, Prevailing Challenges and Future Perspectives.","authors":"Siying Liu, Muyang Yang, Bixin Xi, Yaqin Wang, Ai Zhang, Aiguo Liu, Honglin Jin","doi":"10.1111/imm.70105","DOIUrl":"10.1111/imm.70105","url":null,"abstract":"<p><p>Over the past several decades, cure rates for paediatric hematologic malignancies have improved due to advances in cancer therapy. However, numerous obstacles limit the therapeutic efficacy of paediatric solid tumours, including the tumour's immunosuppressive microenvironment and the lack of specific tumour antigens for targeted therapy. Cancer vaccines, a form of immunotherapy, have been under development for more than half a century. Advances in immunology, materials science, sequencing technologies and bioinformatics have revolutionised cancer vaccine development, achieving substantial success in the prevention and treatment of solid tumours. Despite these achievements, the application of cancer vaccines developed for adults is not fully transferable to paediatric solid tumours because of differences in immune status and metabolic capacity. In clinical practice, most solid tumour vaccines designed for adults are applied directly to paediatric patients without modifications tailored to the unique features of the paediatric immune system. Limited attention has been given to designing cancer vaccines with improved efficacy and reduced toxicity for children and infants. This review discusses paediatric solid tumour vaccines from the immune system against tumour to different antigen types of cancer vaccines, illustrating the unique cancer-immunity cycle of young people and some potential strategies for vaccine modification. Additionally, it discusses the application of paediatric solid tumour vaccines through clinical trial data for conditions such as neuroblastoma, brain tumours and sarcomas. Challenges and potential solutions for enhancing vaccine efficacy, minimising side effects and broadening clinical applications are also addressed.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"38-61"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin Alleviates Chronic Allograft Rejection by Inhibiting Tfh and B Cells While Promoting Treg Cells in Murine Cardiac Transplantation.","authors":"Xiaoyi Shi, Zhe Yang, Wenli Zeng, Chenfang Luo, Jinru Zhang, Changqing Qu, Jianning Wang, Qipeng Sun, Tao Liao","doi":"10.1111/imm.70093","DOIUrl":"10.1111/imm.70093","url":null,"abstract":"<p><p>Follicular helper T (Tfh), B and regulatory T (Treg) cells are involved in the pathogenesis of chronic rejection (CR) after transplantation. Dihydroartemisinin (DHA) is an antimalarial drug with anti-inflammatory activity; however, the effects and mechanisms of DHA on Tfh, B and Treg cells have not been comprehensively elucidated. The aim of this study was to investigate the effect of DHA on Tfh, B and Treg cells and its preventive effect on CR. In vitro assays demonstrated that DHA not only blocks the induction of Tfh cells and alleviates their supportive effect on B cell differentiation but also directly suppresses B cell activation, differentiation and antibody production. Additionally, DHA promotes the induction of Treg cells and enhances their stability in an inflammatory environment. In vivo studies showed that DHA effectively alleviated CR by suppressing neointimal hyperplasia, myocardial injury and interstitial fibrosis and reducing inflammatory cell infiltration and C4d deposition in allografts. Moreover, DHA decreased the levels of Tfh, germinal centre Tfh, B, germinal centre B, IgG-producing and plasma cells in recipients but increased Treg cell levels in recipients and allografts. Mechanistically, we confirmed that DHA inhibits Tfh cells by blocking IL-2-inducible T cell kinase signalling, suppresses B cells by blocking Bruton's tyrosine kinase signalling, and enhances Treg cells by blocking mTOR signalling while promoting STAT5 signalling. In conclusion, our results verified that DHA inhibits Tfh and B cells and enhances Treg cells to attenuate CR in mice, highlighting its potential applicability in the development of robust treatment options.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"136-150"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}