{"title":"New thoughts on the intestinal microbiome-B cell-IgA axis and therapies in IgA nephropathy","authors":"Shaoqing Dang , Xiangyu Zhang , Yuemiao Zhang , Hong Zhang","doi":"10.1016/j.autrev.2025.103835","DOIUrl":"10.1016/j.autrev.2025.103835","url":null,"abstract":"<div><div>IgA nephropathy (IgAN), as the most common chronic glomerulonephritis worldwide, is often triggered by mucosal infections and follows a chronic progression, with the majority of patients ultimately progressing to end-stage renal disease (ESRD) during their lifetimes. Since the mystery of its complete pathogenesis has not been fully solved, the resulting lack of effective early diagnosis and treatment greatly affects the prognosis of patients. Given the well-defined pathological feature of IgA deposition in the mesangial region, the source and role of pathogenic IgA has been focused on. Starting from the microbiology and immunity of the gut, we systematically review both the physiological and the pathological process of microbiome-B cell-IgA axis, from microbial-induced IgA production to the role of IgA in the intestinal immune milieu, and ultimately end up with the various aspects of microbiome-B cell-IgA axis in the pathogenesis of IgAN as well as the corresponding therapeutic initiatives available. Our retrospective review helps researchers to systematically understand the complex role between intestinal flora dysbiosis and pathogenic IgA in IgAN. This understanding provides a foundation for in-depth explorations to uncover more detailed pathogenic mechanisms and to develop more precise and effective diagnostic and therapeutic approaches.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103835"},"PeriodicalIF":9.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966179","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}
Shiran Li , Hongxi Liu , Siyu Zeng , Jingxian Xie , Zhimin Li , Yong Yang , Junlan Chuan
{"title":"Safety of biologics in patients with autoimmune rheumatic diseases during pregnancy: Systematic review and meta-analysis","authors":"Shiran Li , Hongxi Liu , Siyu Zeng , Jingxian Xie , Zhimin Li , Yong Yang , Junlan Chuan","doi":"10.1016/j.autrev.2025.103827","DOIUrl":"10.1016/j.autrev.2025.103827","url":null,"abstract":"<div><h3>Background</h3><div>Patients with autoimmune rheumatic diseases (ARDs) face the dual challenge of controlling disease activity while ensuring fetal safety during pregnancy. Biologics are increasingly used to treat ARDs, but evidence regarding their safety during pregnancy remains uncertain. This study aims to systematically evaluate the safety of biologics during pregnancy by performing a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted in major databases to identify studies involving pregnant ARDs patients treated with biologics from inception to 30th September 2024. The outcomes assessed included small for gestational age (SGA), cesarean section, preterm birth (PTB), low birth weight (LBW), gestational diabetes mellitus (GDM), pre-eclampsia, gestational hypertension, severe maternal infection, birth defects (BD), and a composite outcome of fetal miscarriage or death.</div></div><div><h3>Results</h3><div>A total of 40 studies involving 11,712 patients were included. The pooled prevalence of adverse pregnancy outcomes (APOs) in patients exposed to biologics was comparable to those observed in the general ARDs population. Compared to other biologics, tumor necrosis factor inhibitors (TNFis) was associated with a significantly lower prevalence of cesarean section (26.93 % vs. 63.64 %, <span><math><mi>p</mi></math></span> = 0.01), early pregnancy loss (10.44 % vs. 18.77 %, <span><math><mi>p</mi></math></span> = 0.03), and termination of pregnancy (8.59 % vs. 16.11 %, <span><math><mi>p</mi></math></span> < 0.01). Compared to csDMARDs, biologic use during pregnancy did not significantly increase the risk of APOs.</div></div><div><h3>Conclusion</h3><div>Exposure to biologics during pregnancy in ARDs patients does not significantly increase the risk of APOs, with TNFis showing a well-supported safety profile, while non-TNFi biologics may carry higher risks, requiring cautious evaluation.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103827"},"PeriodicalIF":9.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936245","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":"Interleukin-6 in neuroimmunological disorders: Pathophysiology and therapeutic advances with satralizumab","authors":"Xicheng Li , Chongbo Zhao","doi":"10.1016/j.autrev.2025.103826","DOIUrl":"10.1016/j.autrev.2025.103826","url":null,"abstract":"<div><div>Interleukin-6 (IL-6) is a multifunctional cytokine produced by various cells of the innate and adaptive immune systems. It acts as a regulatory factor in immunity, inflammation, metabolism, and cellular function in multiple organs and systems. The functionality of IL-6 is achieved through multiple signal transduction pathways, such as the JAK/STAT and the NF-κB signaling pathways. In this review, we highlighted the inflammatory and non-inflammatory functions of IL-6, as well as the associated signaling pathways. The involvement of IL-6 in neuroimmunological disorders suggests that the interleukin-6 receptor (IL-6R) monoclonal antibody, satralizumab, is a potential therapeutic strategy. Phase III clinical trials have already validated the safety and efficiency of satralizumab in treating neuromyelitis optica spectrum disorders (NMOSD) and acetylcholine receptor (AChR) seropositive generalized myasthenia gravis (gMG). This review aims to elucidate the pathophysiological role of IL-6, and explore the clinical implications of satralizumab in neuroimmunological diseases, providing insights into its potential therapeutic applications.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103826"},"PeriodicalIF":9.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905881","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":"Adipokines in multiple sclerosis: Immune dysregulation, neuroinflammation, and therapeutic opportunities","authors":"Elham Moases Ghaffary , Geir Bjørklund , Ramesa Shafi Bhat , Omid Mirmosayyeb","doi":"10.1016/j.autrev.2025.103825","DOIUrl":"10.1016/j.autrev.2025.103825","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS), characterized by demyelination, neuroinflammation, and the progressive accumulation of neurologic deficits. Adipose tissue secretes predominantly the bioactive molecules, known as adipokines, which have drawn considerable attention for their roles in modulating immune and metabolic pathways in people with MS (PwMS). Dysregulated adipokines, such as resistin, leptin, and chemerin, induce pro-inflammatory T-cell polarization while deteriorating Blood-Brain Barrier (BBB) integrity. Adiponectin, by contrast, has both immunomodulatory and neuroprotective functions. The opposing functionality highlights the biomarker and the therapeutic potential of adipokines. Preclinical and translational findings have shed light on the role of adipokines in the pathophysiology of MS by influencing T-cell, glial, and BBB functions. In clinical settings, the assessment of adipokines can function as an indicator of prognosis and diagnosis via distinct patterns of expression. In addition, alterations to adipokine profiles through lifestyle changes and pharmaceutical treatment may complement established disease-modifying treatments (DMTs). This study has highlighted the multifaceted role of adipokines in MS management, while further studies exploring the role of adipokine-mediated immunometabolic regulation are suggested.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103825"},"PeriodicalIF":9.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948553","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}
Clément Triaille , Benjamin Terrier , Alice Hadchouel , Elie Haddad , Augusto Vaglio , Marie-Louise Frémond
{"title":"The emerging concept of ANCA-associated vasculitis related to inborn errors of immunity","authors":"Clément Triaille , Benjamin Terrier , Alice Hadchouel , Elie Haddad , Augusto Vaglio , Marie-Louise Frémond","doi":"10.1016/j.autrev.2025.103824","DOIUrl":"10.1016/j.autrev.2025.103824","url":null,"abstract":"<div><div>ANCA-associated vasculitis (AAV) is a group of rare small vessels vasculitis that preferentially affect the kidneys, lungs and upper airways. Although the detailed pathophysiology remains unclear, genetic background has been shown to play a role in sporadic forms of AAV. The discovery of these susceptibility genes (and associated biological pathways) involved in AAV have shaped the current understanding of AAV pathophysiology. In addition to common genetic polymorphisms, specific rare inborn errors of immunity (IEI) have been described with a high frequency of ANCA (antineutrophil cytoplasmic antibodies) positivity and vasculitis features in young individuals (in addition to other manifestations). A systematic literature search revealed that patients with pathogenic variants in <em>COPA, STING1, DNASE1L3,</em> and <em>PIK3CD</em> are at increased risk of developing ANCA and AAV features, including alveolar hemorrhage, interstitial lung disease, pauciimmune glomerulonephritis, and upper airways involvement (septum perforation, saddle-nose deformity, chronic nasal/sinuses ulceration). Some of these IEI may also present with a mixed phenotype and/or auto-antibodies profile associating features of AAV and other autoimmune diseases (in particular systemic lupus erythematosus). Notably, a proportion of reports and series lack serological (ANCA specificity and titers) and/or histopathological data, making challenging to assess the likelihood for ANCA pathogenicity in some patients with IEI (as opposed to unspecific signs of biologic autoimmunity). This point is nonetheless essential to make appropriate therapeutic decisions. In addition, since most of the genes mentioned above are involved in the type 1 interferon signaling, the role of this pathway in AAV etiopathogenesis deserves further investigation.</div><div>In this review, we will describe these IEI, their overlap with sporadic AAV, and their evocative features. Next, we will discuss how these monogenic conditions might inform our general understanding of AAV pathophysiology. We also propose some directions for future research in order to better define the link between ANCA and IEI. Finally, we will consider how making the diagnosis of an IEI in a patient with AAV features might impact individual management.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103824"},"PeriodicalIF":9.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894301","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":"Coffee consumption and risk of multiple sclerosis: A systematic review and meta-analysis","authors":"Mehrad Amirnia , Khazar Raeisnia , Hamidreza Ashayeri , Zahra Hakimzadeh , Ehsan Nasiri , Mahnaz Talebi , Sarvin Sanaie , Amirreza Naseri","doi":"10.1016/j.autrev.2025.103822","DOIUrl":"10.1016/j.autrev.2025.103822","url":null,"abstract":"<div><h3>Background</h3><div>Multiple Sclerosis (MS) is an immune-mediated disease with miscellaneous etiological origins. Given caffeine's neuroprotective and anti-inflammatory attributes and its potential influence on MS risk, and to address the conflict in the clinical evidence, this study aims to comprehensively review the existing literature on the association between coffee consumption and the risk of MS.</div></div><div><h3>Methods</h3><div>Following the PRISMA 2020 guidelines, a systematic search in PubMed, Scopus, Web of Science, and Embase for the studies published up to January 2024 was conducted. Studies that assessed the relationship between coffee intake and the risk of MS were included, and reviews, case reports, non-English papers, in vitro and animal studies, and conference abstracts were excluded. The risk of bias was assessed using the JBI checklists, and meta-analyses were conducted based on odds ratio (OR) using the fourth version of CMA software.</div></div><div><h3>Results</h3><div>Out of 604 initial records, 10 observational studies with 19,430 participants met the inclusion criteria. The included case-control studies showed an overall high quality. Meta-analysis revealed a reduction in MS development in coffee consumers both before (OR: 0.66; 95 % CI: 0.49–0.90; <em>p</em>-value: 0.008; I<sup>2</sup>: 89.65 %; p-value for heterogeneity<0.001) and after adjustment for possible confounders (adjusted OR: 0.42; 95 % CI: 0.20–0.90; p-value: 0.025; I<sup>2</sup>: 89.65 l; p-value for heterogeneity<0.001).</div></div><div><h3>Conclusion</h3><div>Coffee consumption, may decrease the risk of MS; however, further well-designed prospective studies are required to ascertain this association.</div><div>PROSPERO registration number: CRD42023484298.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103822"},"PeriodicalIF":9.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887886","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}
Yuchen Zhao , Tianhao Xu , Zhaoshun Wu , Ning Li , Qianqian Liang
{"title":"Rebalancing redox homeostasis: A pivotal regulator of the cGAS-STING pathway in autoimmune diseases","authors":"Yuchen Zhao , Tianhao Xu , Zhaoshun Wu , Ning Li , Qianqian Liang","doi":"10.1016/j.autrev.2025.103823","DOIUrl":"10.1016/j.autrev.2025.103823","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) arise from the breakdown of immune tolerance to self-antigens, leading to pathological tissue damage. Proinflammatory cytokine overproduction disrupts redox homeostasis across diverse cell populations, generating oxidative stress that induces DNA damage through multiple mechanisms. Oxidative stress-induced alterations in membrane permeability and DNA damage can lead to the recognition of double-stranded DNA (dsDNA), mitochondrial DNA (mtDNA) and micronuclei-DNA (MN-DNA) by DNA sensors, thereby initiating activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. While previous reviews have characterized cGAS-STING activation in autoimmunity, the reciprocal regulation between redox homeostasis and cGAS-STING activation remains insufficiently defined. This narrative review examines oxidative stress-mediated DNA damage as a critical driver of pathological cGAS-STING signaling and delineates molecular mechanisms linking redox homeostasis to autoimmune pathogenesis. Furthermore, we propose therapeutic strategies that combine redox restoration with the attenuation of aberrant cGAS-STING activation, thereby establishing a mechanistic foundation for precision interventions in autoimmune disorders.</div></div><div><h3>Methods</h3><div>The manuscript is formatted as a narrative review. We conducted a comprehensive search strategy using electronic databases such as PubMed, Google Scholar and Web of Science. Various keywords were used, such as \"cGAS-STING,\" \"Redox homeostasis,\" \"Oxidative stress,\" \"pentose phosphate pathway,\" \"Ferroptosis,\" \"mtDNA,\" \"dsDNA,\" \"DNA damage,\" \"Micronuclei,\" \"Reactive oxygen species,\" \"Reactive nitrogen species,\" \"Nanomaterial,\" \"Autoimmune disease,\" \"Systemic lupus erythematosus,\" \"Type 1 diabetes,\" \"Rheumatoid arthritis,\" \"Multiple sclerosis,\" \"Experimental autoimmune encephalomyelitis,\" \"Psoriasis,\" etc. The titles and abstracts were reviewed for inclusion into this review. After removing duplicates and irrelevant studies, 174 articles met inclusion criteria (original research, English language).</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 6","pages":"Article 103823"},"PeriodicalIF":9.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902534","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}
Xinying Qiu , RuiFan Wen , Feifeng Wu , Jueyi Mao , Tasnim Azad , Yang Wang , Junquan Zhu , Xin Zhou , Haotian Xie , Kimsor Hong , Binbin Li , Liang Zhang , Chuan Wen
{"title":"The role of double-negative B cells in the pathogenesis of systemic lupus erythematosus","authors":"Xinying Qiu , RuiFan Wen , Feifeng Wu , Jueyi Mao , Tasnim Azad , Yang Wang , Junquan Zhu , Xin Zhou , Haotian Xie , Kimsor Hong , Binbin Li , Liang Zhang , Chuan Wen","doi":"10.1016/j.autrev.2025.103821","DOIUrl":"10.1016/j.autrev.2025.103821","url":null,"abstract":"<div><div>B cells are essential to the pathophysiology of systemic lupus erythematosus (SLE), a chronic autoimmune illness. IgD-CD27-double negative B cells (DNB cells) are one of the aberrant B cell subsets linked to SLE that have attracted much scientific interest. There is growing evidence that DNB cells play a significant role in the development of the disease and are strongly linked to the activity of lupus. These cells play a pivotal role in the pathogenesis of SLE by producing a diverse array of autoantibodies, which form immune complexes that drive target organ damage. A comprehensive understanding of SLE pathophysiology necessitates in-depth investigation into DNB cells, not only to elucidate their mechanistic contributions but also to uncover novel therapeutic strategies.</div><div>According to available data, treatments that target B cells have proven effective in managing SLE; nevertheless, a significant breakthrough in precision medicine for SLE may come from targeting DNB cells specifically. Despite growing interest in DNB cells, their precise characteristics, developmental trajectories, and regulatory mechanisms remain incompletely defined, posing significant challenges to the field. A comprehensive investigation of the regulatory mechanisms governing DNB cell differentiation and expansion in SLE may facilitate novel therapeutic discoveries. This review aims to provide an updated synthesis of current research on DNB cells, with a focus on their origins, developmental trajectories in SLE, and potential as precision therapeutic targets.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103821"},"PeriodicalIF":9.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876676","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 role of interleukin inhibitors in the treatment of hidradenitis suppurativa; a systematic review of clinical trials","authors":"Nazila Heidari , Amirhossein Heidari , Sara Eghbali , Homayoun Pishraft-sabet , Arman Hajikarim-Hamedani , Yekta Ghane , Zahra Lotfi , Azadeh Goodarzi","doi":"10.1016/j.autrev.2025.103818","DOIUrl":"10.1016/j.autrev.2025.103818","url":null,"abstract":"<div><div>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that presents significant treatment challenges. Recent advancements have enhanced our understanding of its pathophysiology, leading to the development of novel therapeutic strategies. This systematic review evaluates the role of interleukin (IL) inhibitors as emerging treatment options for HS. A systematic search was conducted in PubMed/Medline, Scopus, and Web of Science databases for studies published up to September 2nd, 2024, with inclusion limited to clinical trials available in English. The National Institute of Health (NIH) Quality Assessment Tool for clinical trials and before-after studies with no control group was used to assess the methodological quality of the included studies. Out of 1289 studies, 20 met our inclusion criteria involving 3957 patients. Moreover, four ongoing trials were retrieved from ClinicalTrials.gov. Secukinumab showed sustained hidradenitis Suppurativa Clinical Response (HiSCR) improvements, particularly in biologic-naïve patients with common adverse events (AEs). Bimekizumab was effective with biweekly dosing, while the four-week regimen had inconsistent results, with rare reports of AEs. Brodalumab and bermekimab provided rapid and sustained HiSCR responses with lesion reductions, which were well tolerated. Guselkumab and ustekinumab showed promising but statistically nonsignificant improvements with mild AEs. Risankizumab did not significantly improve HiSCR rates but showed Dermatology Life Quality Index (DLQI) benefits. Anakinra offered moderate efficacy with prolonged exacerbation-free periods but led to some treatment discontinuations. Spesolimab reduced inflammatory lesions and draining tunnels while maintaining a favorable safety profile. IL inhibitors, especially IL-17 inhibitors, have demonstrated efficacy in treating moderate-to-severe HS, while IL-23 inhibitors have shown inconsistent results. Despite their generally favorable safety profiles, further research is needed to optimize treatment strategies and assess long-term outcomes.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103818"},"PeriodicalIF":9.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868284","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}
Siwen Wu , Shubi Zhao , Lei Hai , Ziyin Yang , Shifen Wang , Dawei Cui , Jue Xie
{"title":"Macrophage polarization regulates the pathogenesis and progression of autoimmune diseases","authors":"Siwen Wu , Shubi Zhao , Lei Hai , Ziyin Yang , Shifen Wang , Dawei Cui , Jue Xie","doi":"10.1016/j.autrev.2025.103820","DOIUrl":"10.1016/j.autrev.2025.103820","url":null,"abstract":"<div><div>Macrophages are integral components of the innate immune system, present in nearly all tissues and organs throughout the body. They exhibit a high degree of plasticity and heterogeneity, participating in immune responses to maintain immune homeostasis. When the immune system loses tolerance, macrophages rapidly proliferate and polarize in response to various signaling pathways within a disrupted microenvironment. The direction of macrophage polarization can be regulated by a variety of factors, including transcription factors, non-coding RNAs, and metabolic reprogramming. Autoimmune diseases arise from the immune system's activation against host cells, with macrophage polarization playing a critical role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, such as rheumatoid arthritis, systemic lupus erythematosus, immune thrombocytopenic purpura, and type 1 diabetes. Consequently, elucidating the molecular mechanisms underlying macrophage development and function presents opportunities for the development of novel therapeutic targets. This review outlines the functions of macrophage polarization in prevalent autoimmune diseases and the underlying mechanisms involved. Furthermore, we discuss the immunotherapeutic potential of targeting macrophage polarization and highlight the characteristics and recent advancements of promising therapeutic targets. Our aim is to inspire further strategies to restore macrophage balance in preventing and treating autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103820"},"PeriodicalIF":9.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860079","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}