Autoimmunity reviews最新文献

{"title":"The regulatory roles of Beta-2 glycoprotein I (β2GPI) in thrombosis and hemostasis and abnormal disease conditions developed by autoantibodies against β2GPI","authors":"Ruiying Wang ,&nbsp;Xian Wen Tan ,&nbsp;Chunyan Yu ,&nbsp;Min Li ,&nbsp;Siyu Wang ,&nbsp;Bingshu Yuan ,&nbsp;Xiaoxuan Ma ,&nbsp;Qingping Liu ,&nbsp;Eiji Matsuura ,&nbsp;Lianhua Shen","doi":"10.1016/j.autrev.2025.103984","DOIUrl":"10.1016/j.autrev.2025.103984","url":null,"abstract":"<div><div>Beta-2 glycoprotein I (β2GPI) as a core target antigen of antiphospholipid antibodies (aPLs), is a multifunctional plasma protein with phospholipid-binding properties. Under physiological conditions, β2GPI not only binds to negatively charged phospholipids via its domain V but also interacts with various molecules, such as angiostatin4.5 (AS4.5) and annexin II. These interactions play key roles in maintaining the balance between procoagulant and anticoagulant processes and in promoting angiogenesis. β2GPI binds to pathophysiological ligands, such as apoptotic cells, oxidized low-density lipoprotein (oxLDL) and neutrophil extracellular traps (NETs). These complexes can trigger the production of anti-β2GPI autoantibodies in autoimmune patients, leading to antiphospholipid syndrome (APS). The resulting IgG immune complexes activate and impair endothelial cells, resulting in aberrant activation of the coagulation cascade, disruption of lipid metabolic homeostasis, and breakdown of immune tolerance. Together, these processes promote thrombotic events in APS and accelerate the progression of atherosclerotic plaques. This review paper summaries the dynamic conformational transitions of β2GPI's functional domains that elucidates the dual regulatory role of β2GPI-mediated molecular interactions in thrombosis and atherosclerosis (AS) and reveals the mechanism by which anti-β2GPI autoantibodies mediate endothelial injury, thrombosis, and inflammatory amplification. These findings may provide a theoretical molecular basis for the development of novel diagnostic and therapeutic strategies targeting β2GPI.</div></div><div><h3>Take home message</h3><div><ul><li><span>•</span><span><div>β2GPI maintains the balance between procoagulant and anticoagulant processes and regulates angiogenesis.</div></span></li><li><span>•</span><span><div>Under pathological conditions, immune complexes of β2GPI with multiple molecules such as PS, oxLDL and PF4 drive the pathological cascade of endothelial damage-thrombosis-inflammatory amplification.</div></span></li><li><span>•</span><span><div>Dual-domain targeting (e.g., for stabilizing of DI-DV interaction) to mask antigenicity of β2GPI is potentially useful for inhibiting pathogenic antibody production.</div></span></li></ul></div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103984"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab in glomerular diseases: Indications, long-term use, complications and research gaps","authors":"Joana Gameiro ,&nbsp;Martin Windpessl ,&nbsp;Patrícia Domingues ,&nbsp;Andreas Kronbichler","doi":"10.1016/j.autrev.2025.103937","DOIUrl":"10.1016/j.autrev.2025.103937","url":null,"abstract":"<div><div>Rituximab (RTX) is a monoclonal antibody targeted against the B-cell surface antigen CD20 that plays a significant role in the treatment of glomerular diseases. It is approved for the induction and maintenance of remission of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and it is used as off-label treatment in several other diseases. Despite the increased use, there is a lack of high-quality evidence for some indications. More specifically, the optimal initial dosing and subsequent frequency of administration, if even indicated, remain to be established. There are short and long-term risks associated with its use, including serious infectious complications, late-onset neutropenia, sustained B-cell depletion, hypogammaglobulinemia, and impaired response to vaccines. In this review, we aimed to summarize the indications for RTX use in the management of glomerular diseases, addressed the potential risks of this treatment, and highlighted some knowledge gaps which are unlikely to be answered in future clinical trials. While newer B-cell targeting therapies, including CD20-depleting antibodies, are tested and might be more effective or approved based on randomized controlled trials, RTX will remain relevant due to the limited costs to healthcare providers, the good safety profile and the long-standing experience of glomerular disease physician to use it.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103937"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of GLP-1 analogues on immune-mediated inflammatory diseases: A systematic review","authors":"Chhagan L. Birda ,&nbsp;Fadwa Ibrahim ,&nbsp;Abhirup Chatterjee ,&nbsp;Anuraag Jena ,&nbsp;Vishal Sharma ,&nbsp;Shaji Sebastian","doi":"10.1016/j.autrev.2025.103936","DOIUrl":"10.1016/j.autrev.2025.103936","url":null,"abstract":"<div><h3>Objective</h3><div>Glucagon-like peptide-1 receptor agonists (GLP1RA) are believed to have anti-inflammatory properties apart from antidiabetic and anti-obesity effects.</div></div><div><h3>Methods</h3><div>We performed a systematic review to evaluate the efficacy and safety of GLP1RA in immune-mediated inflammatory disorders (IMIDs). A systematic search was done on 3rd April 2025 in PubMed, Scopus, and Embase for studies reporting the use of GLP1RA among patients with IMIDs. Because of significant heterogeneity and overlapping data originating from the same insurance databases, we decided against performing a data synthesis and meta-analysis. We summarised the data regarding clinical and metabolic outcomes in patients with IMIDs with/without the use of GLP1RA.</div></div><div><h3>Results</h3><div>Thirty-three studies (20 full text, 13 conference abstracts) were included, of which 20 studies focused on inflammatory bowel disease (IBD) and 13 on other IMIDs. Of the three studies reporting on new onset IBD/IMID in GLP1RA users, 2 showed a lower incidence. IBD therapy utilization was reported in 13 studies; steroid use was lower in 5 studies, but the data on the use of biologics were inconclusive. Other outcomes, like hospitalization, IBD complications, surgery, and mortality, seemed to be better in GLP1RA cohorts in a few of the studies. Similarly, psoriasis disease activity-related outcomes were better in the GLP1RA cohort, but the effect on other IMIDs was limited by sparse literature. A total of 12 studies reported metabolic outcomes, including weight loss, glycaemic control, waist circumference, and lipid parameters, all of which showed beneficial effects of GLP1RAs, and these results were comparable to non-IBD/IMID controls. Adverse events (AEs) were reported by 13 studies; gastrointestinal (GI) AEs were higher in the GLP1RA cohort (but the majority were non-severe).</div></div><div><h3>Conclusion</h3><div>GLP1RA use is associated with better disease activity and metabolic outcomes in patients with IMIDs and concomitant metabolic disorders.</div><div>Registration: <span><span>https://osf.io/jvmz6</span><svg><path></path></svg></span></div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103936"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific mechanisms in the pathogenesis and progression of chronic kidney disease","authors":"Guangtao Li ,&nbsp;Zhiwei Xu ,&nbsp;Hongxia Yang ,&nbsp;Dan Zhang ,&nbsp;Bin Liu ,&nbsp;Yifan Song ,&nbsp;Qianhui Li ,&nbsp;Yanghe Zhang ,&nbsp;Honglan Zhou ,&nbsp;Yishu Wang","doi":"10.1016/j.autrev.2025.103938","DOIUrl":"10.1016/j.autrev.2025.103938","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a growing global public health concern, marked by increasing prevalence and substantial economic burden. Notably, CKD demonstrates significant physiological sex differences. Epidemiological evidence indicates that men are more susceptible to developing CKD in early to middle adulthood due to accelerated declines in renal function, whereas postmenopausal women exhibit a sharp rise in CKD incidence and progression. These findings suggest that sex hormones may play a critical regulatory role in CKD pathogenesis. The “bidirectional effects” of sex hormones are considered a fundamental mechanism driving these sex-based disparities. Androgens exacerbate renal inflammation and fibrosis by activating the TGF-β/TNF-α axis and the renin–angiotensin–aldosterone system (RAAS)/20-HETE pathway, in concert with NLRP3 inflammasome activation, thereby worsening glomerular hypertension and metabolic dysfunction. In contrast, estrogens exert protective effects by inhibiting RAAS activity, upregulating the ACE2/Ang-(1–7) pathway, activating the GPER/Sirt1 signaling network, and enhancing antioxidant capacity, thereby preserving renal hemodynamic homeostasis. Furthermore, this review incorporates a range of additional factors—including hormone-like compounds, sex-specific gut microbiota–host metabolic interactions, sex chromosome inactivation or loss, ectopic lipid deposition, and unfavorable lifestyle behaviors—to construct a comprehensive pathological model of sex-specific CKD progression. Elucidating the mechanisms by which sex differences influence kidney disease, and identifying sex-dependent contributors to CKD onset and advancement, may provide critical insights for developing personalized therapeutic strategies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103938"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are the 2023 ACR/EULAR classification criteria a step forward in the management of antiphospholipid syndrome? A literature-based and clinical practice appraisal","authors":"Jaume Alijotas-Reig ,&nbsp;Joana Marques-Soares ,&nbsp;Enrique Esteve-Valverde ,&nbsp;Ariadna Anunciación-Llunell ,&nbsp;Catalina Andrada ,&nbsp;Monika Ockova ,&nbsp;Ariella Hoxha ,&nbsp;Munther A. Khamashta ,&nbsp;Yehuda Shoenfeld ,&nbsp;Francesc Miró-Mur","doi":"10.1016/j.autrev.2025.103956","DOIUrl":"10.1016/j.autrev.2025.103956","url":null,"abstract":"<div><div>Antiphospholipid syndrome (APS) is an autoimmune disease (AID) without defined diagnostic criteria, but having classification criteria, as happens in most AID. Until 2023, we were using 2006 Sydney classification criteria. Although they had a research purposes, in the real life they have been used as a diagnostic tool, equating classification with diagnostic. From July 2023, these criteria were revisited by American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) panel of experts. This recently reported set of classification criteria underlie that only should be used for research purposes. They prioritises specificity ̵ 99 % ̵ at the cost of sensitivity ̵ 84 % ̵ ACR/EULAR criteria consider 6 clinical and 2 laboratory domains. Although new clinical items have been included, improving overall the inclusion of patients and, indirectly diagnosis, i.e., thrombocytopenia, cardiac valvular involvement and microvascular thrombosis, a remarkable number of patients with putative aPL-related disorders could leave out of classification as having APS, and in the real life, losing the opportunity to manage them appropriately. Consequently, these patients will be prone to suffer new events, thrombotic or obstetric, as have been already demonstrated.</div><div>This manuscript focuses on the pros and cons of the clinical and laboratory domains of these new criteria and their impact not only on the clinical point of view, but also in the APS research field.</div><div>Using 6 clinical cases, we provide readers with a sense of diagnostic certainties and uncertainties, and their shortcomings in the context of the ACR/EULAR APS classification.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103956"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTHFR polymorphisms in autoimmune diseases: Mechanistic and clinical perspectives","authors":"Ting Sun ,&nbsp;Yuxian Wu ,&nbsp;Lingyun Kong ,&nbsp;Jingtong Wang ,&nbsp;Feng Zhang ,&nbsp;Yang Liu ,&nbsp;Jie Gao ,&nbsp;Yaoyang Liu","doi":"10.1016/j.autrev.2025.103939","DOIUrl":"10.1016/j.autrev.2025.103939","url":null,"abstract":"<div><div>The methylenetetrahydrofolate reductase (<em>MTHFR</em>) gene encodes a crucial enzyme in folate metabolism, serving as a central regulator of homocysteine homeostasis and one‑carbon metabolic pathways. This review synthesizes current evidence on the mechanistic and clinical implications of two common <em>MTHFR</em> polymorphisms, C677T and A1298C, in autoimmune pathogenesis. We critically examine their contributions to inflammatory responses, endothelial dysfunction, immune imbalance, and epigenetic modifications. Furthermore, we analyze population-specific associations between these variants and susceptibility to eight autoimmune disorders, genotype-phenotype correlations related to clinical manifestations and comorbidities, as well as pharmacogenomic interactions influencing response to methotrexate therapy. By integrating genetic, molecular, and clinical insights, this review highlights the translational potential of <em>MTHFR</em> genotyping for improving risk stratification and personalized treatment strategies in autoimmune and immune-mediated inflammatory conditions.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103939"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-induced inflammatory arthritis vs rheumatoid arthritis: A comparative review","authors":"Iliopoulos Georgios ,&nbsp;Sideridou Fani ,&nbsp;Bogdanos Dmitrios ,&nbsp;Liew David ,&nbsp;Daoussis Dimitrios","doi":"10.1016/j.autrev.2025.103943","DOIUrl":"10.1016/j.autrev.2025.103943","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of oncology but are frequently accompanied by immune-related adverse events (irAEs). Among these, ICI-induced inflammatory arthritis (ICI-IA) has emerged as the most common musculoskeletal toxicity, often mimicking rheumatoid arthritis (RA) in its clinical and imaging features. This narrative review synthesizes current evidence comparing ICI-IA with RA across epidemiology, pathophysiology, clinical presentation, imaging, treatment, and prognosis. While both entities share overlapping manifestations such as polyarthritis, synovitis, and joint erosions, ICI-IA is typically seronegative, arises subacutely after ICI initiation, and exhibits distinct immunopathologic signatures, including cytotoxic CD8+ T-cell predominance and unique B-cell alterations. ICI-IA may persist after ICI cessation, with chronic disease linked to improved oncologic outcomes. Therapeutic strategies require balancing arthritis control and preservation of anti-tumor immunity. Glucocorticoids and conventional disease modifying anti-rheumatic drugs (cDMARDs) are key players with proven safety and efficacy, whereas biologic therapies remain reserved for severe or refractory cases mainly due to cancer progression concerns. Furthermore, early rheumatology referral improves patient outcomes and reduces glucocorticoid exposure. Understanding the differences between ICI-IA and RA is essential for optimizing diagnosis, guiding individualized approach and applying precision medicine at the crossroads of oncology and rheumatology.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103943"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VE/VCO2 at ventilatory threshold and peak VO2 in CPET studies of patients with scleroderma-associated PAH: A systematic review and meta-analyses","authors":"Julie Better ,&nbsp;Sylvie Leroy ,&nbsp;Maarten K. Ninaber ,&nbsp;Georgia Trakada ,&nbsp;Bilge Kesikburun ,&nbsp;Stephan Rosenkranz ,&nbsp;Ralph Ewert ,&nbsp;Dirk Habedank ,&nbsp;Daniel Dumitrescu ,&nbsp;Yanis Kouchit ,&nbsp;Nihal Martis","doi":"10.1016/j.autrev.2025.103942","DOIUrl":"10.1016/j.autrev.2025.103942","url":null,"abstract":"<div><h3>Context</h3><div>Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Cardiopulmonary exercise testing (CPET) has been studied to detect SSc-associated PAH.</div></div><div><h3>Objectives</h3><div>To evaluate the diagnostic value of the ventilatory equivalent for CO₂ at anaerobic or ventilatory threshold [VE/VCO₂(VeT)] and peak oxygen uptake (peak VO₂) for SSc-associated PAH obtained by CPET.</div></div><div><h3>Methods</h3><div>A systematic database search from 1993 to 2024 and meta-analyses were performed according to PRISMA guidelines to include original studies relating to SSc and CPET reporting VE/VCO₂(VeT) and peak VO₂. The random-effects model was chosen for the meta-analyses studying VE/VCO₂(VeT), indexed and predicted percentage (%pred.) peak VO₂, respectively. Meta-regression was only performed for VE/VCO₂(VeT) with covariates defined as the percentage of limited cutaneous disease, percentage of interstitial lung disease, and %pred. of peak VO₂.</div></div><div><h3>Results</h3><div>Out of 206 studies, 941 SSc patients from 15 studies were included. VE/VCO₂(VeT) (11 studies, <em>n</em> = 850) was statistically lower in patients without PAH (32.68 ± 5.42 vs. 39.81 ± 9.32) with a mean effect size of −1.182 (95 %CI, −1.691 to −0.672; <em>p</em> &lt; 0.001) (I² = 86 %). The mean effect size for weight-indexed peak VO₂ (11 studies, <em>n</em> = 848) was 0.713 (95 %CI, 0.371 to 1.054; <em>p</em> &lt; 0.001) with higher values in patients without PAH (16.47 ± 4.62 vs. 13.61 ± 4.16 mL/kg/mn) (I² = 70 %). Similarly, the mean effect size for %pred. Peak VO₂ (12 studies, <em>n</em> = 850) was 0.659 (95 %CI, 0.425 to 0.894; p &lt; 0.001) reflecting higher values in patients without PAH (74.00 ± 17.50 vs. 54.84 ± 18.14 %pred.) (I² = 37 %). Meta-regression analysis of data from 7 studies did not yield significant <em>p</em> values for the covariates.</div></div><div><h3>Conclusions</h3><div>The effect size of each meta-analysis indicates that higher VE/VCO₂(VeT) and lower peak VO₂ may be considered as independent CPET markers of PAH in patients with SSc. CPET is a non-invasive and safe procedure for exploring dyspnoea in patients with SSc and, in association with conventional imaging techniques, may provide a reliable assessment of the presence of PAH.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103942"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental toxins and toxic metals in autoimmune diseases: Sex differences, hormonal influences, and immune dysregulation","authors":"Geir Bjørklund ,&nbsp;David R. Wallace ,&nbsp;Kimiya Kangarlou ,&nbsp;Fahimida Hossain ,&nbsp;Massimiliano Peana","doi":"10.1016/j.autrev.2025.103955","DOIUrl":"10.1016/j.autrev.2025.103955","url":null,"abstract":"<div><div>Environmental toxins, including toxic metal(<em>oid</em>)s such as mercury, lead, cadmium, and arsenic, as well as endocrine-disrupting chemicals like bisphenol A and phthalates, play a critical role in the onset and progression of autoimmune diseases. These substances accumulate in biological tissues and disrupt immune homeostasis through oxidative stress, molecular mimicry, and epigenetic modifications, mechanisms that contribute to autoantibody production and chronic inflammation, hallmarks of autoimmunity. Women are disproportionately affected by autoimmune diseases due to inherent differences in immune function, hormonal regulation, and genetic susceptibility. Estrogen, a key immunomodulatory hormone, can amplify immune responses and promote autoantibody generation. Its interaction with environmental toxins further exacerbates immune dysregulation, increasing female vulnerability to conditions such as systemic lupus erythematosus, rheumatoid arthritis, and autoimmune thyroid disorders. Hormonal fluctuations during puberty, pregnancy, and menopause additionally influence toxin metabolism and detoxification efficiency, compounding the risk of immune imbalance and disease onset in women. This review synthesizes current evidence on the mechanisms through which environmental toxicants contribute to autoimmune pathogenesis, with particular focus on sex-specific vulnerabilities. It explores the role of hormonal-immune-environment interactions across the female lifespan and highlights emerging research on epigenetic inheritance, gut dysbiosis, and biomarker development. By integrating mechanistic, epidemiological, and clinical findings, this review aims to inform targeted strategies for prevention, early detection, and risk reduction of environmentally driven autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103955"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Trm-Treg Axis as a tissue-encoded immune checkpoint in chronic inflammation and autoimmunity","authors":"Liang Li ,&nbsp;Yumin Xia ,&nbsp;Yale Liu","doi":"10.1016/j.autrev.2025.103977","DOIUrl":"10.1016/j.autrev.2025.103977","url":null,"abstract":"<div><div>Tissue-resident memory T (Trm) cells, once heralded as gatekeepers of localized immune protection, have emerged as central players in the pathogenesis of chronic inflammation and autoimmunity at epithelial barriers. At the heart of this immunological paradox lies the dynamic interplay between Trm and regulatory T (Treg) cells—a tissue-encoded checkpoint that calibrates immune defense against the need for tolerance and repair. Disruption of this axis unleashes the latent pathogenicity of Trm cells, fueling persistent inflammation, epithelial dysfunction, and disease relapse. Here, we propose that the Trm-Treg interaction acts as a molecular rheostat that tunes immune homeostasis at barrier sites. We dissect the tissue-specific mechanisms that sustain this alliance, highlight its failure in diseases such as inflammatory bowel disease (IBD), psoriasis, and chronic obstructive pulmonary disease (COPD), and explore emerging therapeutic strategies aimed at recalibrating this immune checkpoint to restore durable epithelial tolerance.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103977"},"PeriodicalIF":8.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}