Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-22DOI: 10.1016/j.autrev.2025.103887
Daniel Guimarães de Oliveira , Zoe Karakikla-Mitsakou , Lena Koskina , Laurent Arnaud
{"title":"Social determinants of health and disparities across the Patient pathway in Systemic Lupus Erythematosus: a narrative review","authors":"Daniel Guimarães de Oliveira , Zoe Karakikla-Mitsakou , Lena Koskina , Laurent Arnaud","doi":"10.1016/j.autrev.2025.103887","DOIUrl":"10.1016/j.autrev.2025.103887","url":null,"abstract":"<div><h3>Objective</h3><div>Systemic Lupus Erythematosus (SLE) is a complex, chronic autoimmune disease with significant heterogeneity in its presentation and progression. Social determinants of health (SDH), including socioeconomic factors, health literacy and access to care, among others, can shape SLE outcomes. This review explores the impact and interaction of these factors across the entire lupus patient pathway – from presentation to therapeutic management and outcomes - and proposes targeted solutions to improve health equity and patient outcomes in SLE.</div></div><div><h3>Methods</h3><div>Narrative review, synthesizing findings from peer-reviewed studies published in the last decade, focusing on SDH influencing SLE outcomes.</div></div><div><h3>Results</h3><div>SDH were found to consistently influence the entirety of the SLE patient pathway. Lupus patients from lower socioeconomic backgrounds experience increased diagnostic delay, worse damage accrual and higher mortality rates. Health literacy emerged as a critical factor, with tailored educational interventions shown to improve therapeutic adherence. Geographic disparities were also significant, with persons living in rural areas reporting reduced access to specialist care compared to urban counterparts. Interventions addressing financial barriers, transportation assistance and remote healthcare options demonstrated potential to improve access and outcomes. Additional approaches are proposed, that take into account the intersection of multiple vulnerabilities, their correlation and their interaction with individual lupus characteristics, which result in cumulative effects on disease severity.</div></div><div><h3>Conclusions</h3><div>Social determinants of health have a profound and measurable impact on SLE outcomes, highlighting the need for multidisciplinary approaches to reduce disparities. Evidence supports targeted interventions aimed at answering local and individual patient contexts, but also multi-level policy changes that address the complexity of these determinants' intersections, to reduce disparities and improve lupus patient outcomes overall. Further studies are critically needed to understand the broader geographic and cultural implications of these social determinants, and longitudinal research should prioritize evaluating the implementation and scalability of strategies addressing these factors.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103887"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703269","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-17DOI: 10.1016/j.autrev.2025.103885
Yutong Liu , Xueling Jiang , Songnian Zhuang , Lihua Zhu , Bo Zhu , Ke Rui , Jie Tian
{"title":"Itaconate: A key regulator of immune responses and potential therapeutic target for autoimmune and inflammatory diseases","authors":"Yutong Liu , Xueling Jiang , Songnian Zhuang , Lihua Zhu , Bo Zhu , Ke Rui , Jie Tian","doi":"10.1016/j.autrev.2025.103885","DOIUrl":"10.1016/j.autrev.2025.103885","url":null,"abstract":"<div><div>Itaconate, a metabolite of the tricarboxylic acid cycle (TAC), has gained increasing attention in recent years due to its anti-inflammatory and immunomodulatory properties. It plays a crucial role in immune regulation by modulating signal transduction and posttranslational modification. Itaconate is derived from cis-aconitate decarboxylation and is produced by cis-aconitate decarboxylase (ACOD1) in the mitochondria. During cellular stress conditions, itaconate rapidly accumulates in myeloid cells. Recent studies have demonstrated that itaconate plays a pivotal role in modulating both innate and adaptive immune responses. Moreover, itaconate regulates the differentiation and function of innate immune and lymphoid cells, which is implicated in the pathogenesis of autoimmune diseases. In this review, we aim to explore the recent advancements in comprehending the functional regulation and mechanisms of itaconate in various populations of innate immune and lymphoid cells, as well as its immunomodulatory effects in the development of autoimmune diseases. In addition, we highlight the potential therapeutic applications of itaconate and its derivatives in autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103885"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665972","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-14DOI: 10.1016/j.autrev.2025.103876
Jin Lin , Fan Yang , Yanyi Zheng , Xianglin Wang , Xiaoli Fan , Li Yang
{"title":"Glycometabolic reprogramming of immune cells in autoimmune diseases","authors":"Jin Lin , Fan Yang , Yanyi Zheng , Xianglin Wang , Xiaoli Fan , Li Yang","doi":"10.1016/j.autrev.2025.103876","DOIUrl":"10.1016/j.autrev.2025.103876","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) are a classification of disorders that occur owing to the breakdown of immunological tolerance to self-antigens, leading to an immune response to these antigens and associated bodily harm. The pathogenesis and etiology of these diseases remain unclear. A growing body of research indicates that metabolic reprogramming of immune cells is crucial for immunological control. In particular, glycolysis, a crucial metabolic process in cells, is reconfigured to influence the phenotypic and function of immune cells, therefore playing a role in the onset and progression of ADs. This review elaborates on the involvement of glycometabolic reprogramming in ADs and explores the function of glycometabolic reprogramming in immune cells throughout disease progression. Furthermore, we examine the principal targets implicated and their influence on disease advancement. Finally, we provide a brief summary and outlook of studies related to glycometabolic reprogramming of immune cells in ADs, aiming to guide therapeutic strategies for these diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103876"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648353","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-08DOI: 10.1016/j.autrev.2025.103872
Yuezheng Xiao , Yue Xin , Kai Shen , Ming Yang , Haijing Wu
{"title":"The roles of transient receptor potential vanilloid in autoimmune diseases","authors":"Yuezheng Xiao , Yue Xin , Kai Shen , Ming Yang , Haijing Wu","doi":"10.1016/j.autrev.2025.103872","DOIUrl":"10.1016/j.autrev.2025.103872","url":null,"abstract":"<div><div>The transient receptor potential vanilloid (TRPV) is a family of tetrameric cation channels, expressed in various tissues and cell types. It includes thermosensitive isoforms (TRPV1–4) and calcium-permeable members (TRPV5–6). In the context of autoimmune diseases, TRPV channels have been firmly established as pivotal regulators that bridge changes in the cellular environment to the immune system.</div><div>Originally identified for their roles in thermosensation and nociception, these polymodal sensors have now emerged as crucial determinants of immune cell function. They are capable of converting chemical signals, temperature fluctuations, and mechanical forces into calcium-mediated signal transduction pathways. Mounting evidence indicates that dysregulated TRPV channel activity leads to pathological calcium influx, triggering a signaling cascade that reprograms the functions of key immune cells and modulates pain and itch signaling through neuroimmune crosstalk. These cascades amplify inflammatory responses, exacerbate autoimmune pathology, promote inflammatory cytokine release, and modulate pain/itch signaling via neuroimmune crosstalk.</div><div>Specifically, these mechanisms are instrumental in the progression including autoimmune disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), multiple sclerosis (MS), psoriasis, and atopic dermatitis (AD). Novel therapeutic strategies are emerging, aiming to modulate TRPV activity in autoimmune conditions. Approaches include suppressing hyperactive channels and leveraging their immunoregulatory potential. Promising preclinical results have highlighted that TRPV channels exhibit dual translational potential in mechanistic research of autoimmune diseases, integrating precise targeting with dynamic monitoring capabilities. However, translating these findings into clinical applications faces significant challenges, including differential effects on neuronal and immune signaling, as well as systemic side effects caused by disruptions to physiological homeostasis.</div><div>This narrative review discuss how TRPV channel signaling has enhanced our understanding of autoimmune disease initiation. By dissecting how TRPV-mediated immune dysregulation drives pathological immune responses, we seek to offer novel mechanistic insights to inform the development of more effective and comprehensive treatment strategies for autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103872"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607262","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-17DOI: 10.1016/j.autrev.2025.103882
Keda Chen , Zhiyi Wang , Jiaxuan Li , Yutong Xu , Siyi Gu , Hongyu Li , Jianhua Li , Yanjun Zhang , Naihui Mao
{"title":"Chronic inflammation in Long COVID relationship to autoimmune diseases","authors":"Keda Chen , Zhiyi Wang , Jiaxuan Li , Yutong Xu , Siyi Gu , Hongyu Li , Jianhua Li , Yanjun Zhang , Naihui Mao","doi":"10.1016/j.autrev.2025.103882","DOIUrl":"10.1016/j.autrev.2025.103882","url":null,"abstract":"<div><div>The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103882"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666970","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-16DOI: 10.1016/j.autrev.2025.103884
Qingmiao Zhu , Xiaolong Li , Ting Zhao
{"title":"Authors' response to “comment on ‘systemic lupus erythematosus and male reproductive health: A systematic review and meta-analysis’”","authors":"Qingmiao Zhu , Xiaolong Li , Ting Zhao","doi":"10.1016/j.autrev.2025.103884","DOIUrl":"10.1016/j.autrev.2025.103884","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103884"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658245","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-16DOI: 10.1016/j.autrev.2025.103883
Tengyue Wang , Hongli Wang , Rui Lv , Chengping Wen , Mingzhu Wang , Lin Huang
{"title":"The role of γδ T cells and CAR-γδ T cell therapy in autoimmune diseases","authors":"Tengyue Wang , Hongli Wang , Rui Lv , Chengping Wen , Mingzhu Wang , Lin Huang","doi":"10.1016/j.autrev.2025.103883","DOIUrl":"10.1016/j.autrev.2025.103883","url":null,"abstract":"<div><div>Autoimmune diseases represent a major global health challenge, imposing substantial economic, social, and personal burdens on human society. γδ T lymphocytes are a unique T cell subset that bridges innate and adaptive immunity, demonstrating remarkable characteristics in immune regulation and inflammatory modulation. In this context, Chimeric Antigen Receptor (CAR)-γδ T cell therapy emerges as a promising immunotherapeutic strategy with transformative potential in addressing autoimmune disorders. This review comprehensively explores the multifaceted roles of γδ T lymphocytes in autoimmune pathogenesis, highlighting their distinctive functions and properties. It discusses the potential and advantages of applying γδ T cells to CAR-T cell therapy, elucidating the prospects of treating autoimmune diseases through CAR-γδ T cell therapy in the future.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103883"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666971","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-10DOI: 10.1016/j.autrev.2025.103875
M. Mané-Damas , A.K. Schöttler , F. Marcuse , P.C. Molenaar , T. Mohile , J.G.J. Hoeijmakers , M. Hochstenbag , J. Damoiseaux , J.G. Maessen , M. Abdul-Hamid , A. zur Hausen , M.H. de Baets , M. Losen , P. Martinez-Martinez
{"title":"Myasthenia gravis with antibodies against the AChR, current knowledge on pathophysiology and an update on treatment strategies with special focus on targeting plasma cells","authors":"M. Mané-Damas , A.K. Schöttler , F. Marcuse , P.C. Molenaar , T. Mohile , J.G.J. Hoeijmakers , M. Hochstenbag , J. Damoiseaux , J.G. Maessen , M. Abdul-Hamid , A. zur Hausen , M.H. de Baets , M. Losen , P. Martinez-Martinez","doi":"10.1016/j.autrev.2025.103875","DOIUrl":"10.1016/j.autrev.2025.103875","url":null,"abstract":"<div><div>Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder where the neuromuscular transmission is impaired, causing symptoms of skeletal muscle weakness and fatigue. The presence of autoantibodies against the muscle nicotinic acetylcholine receptor (AChR) is the most prevalent cause of MG. Abnormalities in the thymus are common in AChR-MG, and thymectomy has proven to be therapeutically beneficial. Up to 30 % of AChR-MG patients have also thymoma. Moreover, patients with thymoma without MG are more prompt to develop MG compared to the general population.</div><div>Autoantibodies in AChR-MG damage the postsynaptic membrane of the neuromuscular junction (NMJ) and cause muscle weakness by impairing synaptic transmission because of the depletion of the AChRs and destruction of the NMJ. The pathogenic autoantibody levels vary greatly between patients. In contrast, in individual patients changes in autoantibody levels correlate well with disease severity. A small selection of patients has been used to exemplify the individual relationship between autoantibody levels and disease progression. The study of the effector functions of the autoantibodies and the compensatory mechanisms at the NMJ are important to select the best treatment strategy for each patient. Even though classical immunomodulatory treatments are effective in many patients, around 10–20 % of patients do not respond to current therapies. This may be attributed to the production of autoantibodies by different circulating cells including mature B and long-lived plasma cells, which are resistant to most commonly used immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected refractory patients.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103875"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616106","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-14DOI: 10.1016/j.autrev.2025.103879
Nantakarn Pongtarakulpanit , Shiri Keret , Vaidehi Kothari , Francisca Bozán , Chengappa Kavadichanda , Akira Yoshida , Valérie Leclair , Anuradha Bishnoi , Kaveh Ardalan , Edoardo Conticini , Ting-Yuan Lan , Océane Landon-Cardinal , Iris Y.K. Tang , Silvia Rosina , Belina Y. Yi , James B. Lilleker , Eduardo Dourado , Prateek C. Gandiga , Rohit Aggarwal
{"title":"Remission and low disease activity definitions in adult idiopathic inflammatory myopathies: A narrative review by myositis clinical trials consortium (MCTC)","authors":"Nantakarn Pongtarakulpanit , Shiri Keret , Vaidehi Kothari , Francisca Bozán , Chengappa Kavadichanda , Akira Yoshida , Valérie Leclair , Anuradha Bishnoi , Kaveh Ardalan , Edoardo Conticini , Ting-Yuan Lan , Océane Landon-Cardinal , Iris Y.K. Tang , Silvia Rosina , Belina Y. Yi , James B. Lilleker , Eduardo Dourado , Prateek C. Gandiga , Rohit Aggarwal","doi":"10.1016/j.autrev.2025.103879","DOIUrl":"10.1016/j.autrev.2025.103879","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare systemic autoimmune rheumatic diseases. Despite advances in treatment, the definition of remission and low disease activity (LDA) in IIM remains inconsistent and lacks consensus and validation. This review summarizes existing published definitions, achievement rates, and predictive factors of remission/LDA in adult IIM, focusing on dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathies (IMNM). Our literature review revealed a wide variability in remission definitions, incorporating physician assessment, muscle strength, laboratory normalization, and medication tapering or discontinuation. Some studies defined “remission on medication”, while others required complete treatment cessation. Most definitions required a minimum duration of six months. Organ-specific remission (including for the skin, lung, and muscle domains) was inconsistently addressed. LDA has been less extensively studied in IIM, with the myositis disease activity assessment visual analog scales (MYOACT) being the only measure applied to DM. Remission rates varied widely, with stricter criteria yielding lower rates. Factors associated with remission included younger age, early immunosuppressive treatment, non-severe muscle involvement, the absence of myositis-specific autoantibodies (MSA), although some studies reported positivity for certain MSA were associated with remission. Conversely, remission was less likely for patients with PM, overlap myositis, and those positive for anti-TIF1-γ or Ku autoantibodies. Standardized remission criteria incorporating physician assessment, patient assessment, organ-specific parameters, laboratory assessments, and sustained remission duration are essential for harmonizing clinical and research evaluations in IIM. Establishing uniform definitions will improve therapeutic outcome assessments and facilitate meaningful comparisons in clinical trials and real-world practice.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103879"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648354","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}
Autoimmunity reviewsPub Date : 2025-09-24Epub Date: 2025-07-14DOI: 10.1016/j.autrev.2025.103878
Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou
{"title":"The FOXO1-SIRT1 axis in ankylosing spondylitis: A cross-platform regulator linking immunometabolism, oxidative stress, and bone remodeling","authors":"Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou","doi":"10.1016/j.autrev.2025.103878","DOIUrl":"10.1016/j.autrev.2025.103878","url":null,"abstract":"<div><div>Ankylosing spondylitis (AS) is a chronic immune-mediated disorder defined by the paradoxical coupling of inflammatory bone erosion and ectopic new bone formation. Recent studies implicate the Forkhead box O1 (FOXO1)-Sirtuin 1 (SIRT1) signaling axis as a systems-level regulator integrating immune metabolism, redox balance, and skeletal remodeling. FOXO1 and SIRT1 cooperatively regulate immune tolerance, redox balance, and skeletal homeostasis via transcriptional, epigenetic, and metabolic pathways.</div><div>This review delineates the cross-platform roles of the FOXO1-SIRT1 axis across three interrelated modules: regulation of immune cell metabolism and polarization; redox sensing and organelle quality control via autophagy and mitophagy; and coordination of osteoblast – osteoclast dynamics in inflammatory microenvironments. Dysregulation of this axis disrupts immuno-metabolic equilibrium and promotes pathological ossification, contributing to the dual pathology of AS.</div><div>We further discuss emerging therapeutic strategies – ranging from SIRT1 activators and anti -Interleukin-17 A (IL-17 A) biologics to histone deacetylase inhibitors – that converge mechanistically on FOXO1-SIRT1 signaling. These translational approaches underscore the axis's potential as a cross-domain integrator of immune and skeletal homeostasis, and as a promising target for precision intervention in AS.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103878"},"PeriodicalIF":9.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648355","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}