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Current Opinion in Immunology最新文献

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Rheumatoid arthritis — the role of T cells in this complex systemic autoimmune disease 类风湿关节炎- T细胞在这种复杂的系统性自身免疫性疾病中的作用
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-09 DOI: 10.1016/j.coi.2025.102555
Christina S Savvides , Eddie A James , Jane H Buckner
{"title":"Rheumatoid arthritis — the role of T cells in this complex systemic autoimmune disease","authors":"Christina S Savvides ,&nbsp;Eddie A James ,&nbsp;Jane H Buckner","doi":"10.1016/j.coi.2025.102555","DOIUrl":"10.1016/j.coi.2025.102555","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that can affect individuals at any age of life. While involvement of the immune system in RA has long been clear, current treatments remain limited to interventions that broadly suppress immune responses with a lack of personalization. This review highlights recent advances in our understanding of immune dysregulation in RA in three settings: (1) before disease onset; (2) in synovial tissue the site of inflammation; and (3) during disease flares after drug withdrawal. These findings provide a detailed view of T cell subsets correlated with the presence or imminent onset of RA, which provides guidance for future investigations to validate new biomarkers that would allow clinicians to diagnose and intercede earlier. It suggests mechanisms that could be leveraged for novel targeted therapeutic approaches and individualized precision treatment wherein clinicians would be able to predict effective treatments for each patient.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102555"},"PeriodicalIF":6.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity 促进自身免疫中调节性T细胞功能的药物治疗策略
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-04 DOI: 10.1016/j.coi.2025.102554
Robert C Wright , Daniel J Campbell , Megan K Levings
{"title":"Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity","authors":"Robert C Wright ,&nbsp;Daniel J Campbell ,&nbsp;Megan K Levings","doi":"10.1016/j.coi.2025.102554","DOIUrl":"10.1016/j.coi.2025.102554","url":null,"abstract":"<div><div>Autoimmune diseases arise when self-antigen-specific T and B cells escape central and peripheral mechanisms of tolerance. One such mechanism is control of autoreactivity by regulatory T cells (Tregs), which have an essential role in suppressing autoimmunity. Consequently, there is significant interest in developing ways to boost or restore the function of Tregs in order to prevent or treat autoimmunity, induce tolerance, and thus reduce the reliance on broadly immunosuppressive agents. Strategies include enhancing the numbers and/or function of Tregs directly <em>in vivo</em> or via adoptive cell therapy. Here, we review recent advances in our understanding of how pharmacologic approaches can be applied to enhance Treg function <em>in vivo</em> through repurposing of established drug therapies or application of new therapies. Specifically, we discuss the potential of Treg-promoting drugs, including interleukin-2 and its derivatives, and tumor necrosis factor receptor 2 agonists, as well as Treg-preserving tyrosine kinase 2 inhibitors. We discuss how co-stimulatory blockade with CTLA-4 immunoglobulin affects tolerogenic environments and consider whether lymphodepleting therapies, such as antithymocyte globulin and teplizumab, might be needed to condition the environment for better Treg-promoting effects. We focus on the potential application of Treg-promoting drugs in type 1 diabetes and draw on evidence from transplantation. With multiple pharmacotherapeutic strategies to optimize Tregs <em>in vivo</em>, there is significant promise for new approaches to effectively and durably induce autoimmune disease remission.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102554"},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The intestinal microbiome in type 1 diabetes: bridging early childhood exposures with translational advances 1型糖尿病的肠道微生物组：用转化进展架起儿童早期暴露的桥梁
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.coi.2025.102553
Furkan Guvenc , Jayne S Danska
{"title":"The intestinal microbiome in type 1 diabetes: bridging early childhood exposures with translational advances","authors":"Furkan Guvenc ,&nbsp;Jayne S Danska","doi":"10.1016/j.coi.2025.102553","DOIUrl":"10.1016/j.coi.2025.102553","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) results from T cell–mediated destruction of pancreatic β-cells, requiring lifelong insulin therapy and glycemic monitoring. While genetic risk, particularly HLA class II, is well established, rising T1D incidence and earlier onset suggest environmental modifiers. Mouse models show that microbiome alterations influence β-cell autoimmunity, and human studies link microbiome composition to T1D, though specific microbial regulators remain unidentified. We examine host–microbiome interactions, including studies implicating enteroviruses in modulating islet autoimmunity. Mechanistic discoveries of microbial effects on diabetes have emerged from mouse model studies. We consider clinical applications, including microbiota-targeted therapies and biomarkers of microbiome-immune crosstalk. Future research should integrate microbial, genetic, environmental, and immune data using multi-omic approaches. Collaborative efforts combining immunology, microbiology, and clinical metadata will drive discovery and precision medicine in T1D.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102553"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing microglia-based cell therapies for the treatment of neurodegenerative diseases 利用小胶质细胞疗法治疗神经退行性疾病
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-03-25 DOI: 10.1016/j.coi.2025.102552
Adeline E Walsh , John R Lukens
{"title":"Harnessing microglia-based cell therapies for the treatment of neurodegenerative diseases","authors":"Adeline E Walsh ,&nbsp;John R Lukens","doi":"10.1016/j.coi.2025.102552","DOIUrl":"10.1016/j.coi.2025.102552","url":null,"abstract":"<div><div>Given the growing evidence linking microglia to the onset and progression of various neurodegenerative diseases, these brain-resident macrophages have emerged as a promising cell type for targeted therapeutic interventions. This review highlights recent studies that utilized innovative, microglia-focused strategies for the treatment of diverse neurodegenerative disorders including lysosomal storage disorders, granulin frontotemporal dementia, and Alzheimer’s disease. Cutting-edge therapeutic strategies range from replacing faulty microglia with peripheral macrophage precursors or induced human pluripotent stem cell–derived microglia to engineering microglia that target toxic aggregates or deliver remediating payloads. We also examine the potential limitations as well as the clinical benefits of these strategies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102552"},"PeriodicalIF":6.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The choroid plexus: a command center for brain–body communication during inflammation 脉络膜丛：炎症期间脑-体交流的指挥中心
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102540
Huixin Xu, Christine Hehnly, Maria K Lehtinen
{"title":"The choroid plexus: a command center for brain–body communication during inflammation","authors":"Huixin Xu,&nbsp;Christine Hehnly,&nbsp;Maria K Lehtinen","doi":"10.1016/j.coi.2025.102540","DOIUrl":"10.1016/j.coi.2025.102540","url":null,"abstract":"<div><div>During brain inflammation, rigorous regulation of brain–body communication is required for sufficient, but not excessive, immune activation. As a crucial neuroimmune interface, the choroid plexus (ChP) epithelium serves as both a physical barrier between blood and cerebrospinal fluid (CSF) and a gateway allowing peripheral immune cell entry into the central nervous system (CNS). Recent years have witnessed increasing investigations of ChP events during brain inflammation. Here, we contextualize new findings with established ChP core functions, including CSF secretion and blood–CSF barrier regulation. We reason that the ChP is an organ where immune and nonimmune cells collaborate to defend the CNS. We discuss the pertinent mechanisms and the implications for neurologic disease etiology and treatment. Finally, we discuss outstanding questions for this rapidly expanding field and suggest key technologies and experimental steps to elucidate the full range of ChP functions during neuroinflammatory conditions, such as infection, injury, and aging.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"93 ","pages":"Article 102540"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Primary atopic disorders: inborn errors of immunity causing severe allergic disease 原发性特应性疾病：先天性免疫缺陷导致严重过敏性疾病
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102538
Maryam Vaseghi-Shanjani , Simran Samra , Pariya Yousefi , Catherine M Biggs , Stuart E Turvey
{"title":"Primary atopic disorders: inborn errors of immunity causing severe allergic disease","authors":"Maryam Vaseghi-Shanjani ,&nbsp;Simran Samra ,&nbsp;Pariya Yousefi ,&nbsp;Catherine M Biggs ,&nbsp;Stuart E Turvey","doi":"10.1016/j.coi.2025.102538","DOIUrl":"10.1016/j.coi.2025.102538","url":null,"abstract":"<div><div>Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and food allergies, are driven by dysregulated immune responses, often involving IgE-mediated mast cell and basophil activation, Th2 inflammation, and epithelial dysfunction. While environmental factors are well-known contributors, the genetic components underpinning these conditions are increasingly understood. Traditionally viewed as polygenic multifactorial disorders, allergic diseases can also be caused by single-gene defects affecting the immune system and skin epithelial barrier, leading to profoundly dysregulated allergic responses. These monogenic allergic disorders are collectively referred to as primary atopic disorders or PADs. To date, over 48 single-gene defects have been established to cause PADs. This review highlights (i) the significance of PADs, (ii) the biological pathways involved in the pathogenesis of PADs, (iii) clinical strategies to differentiate PADs from their much more common polygenic counterparts, and (iv) diagnostic strategies for PADs.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102538"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
More X’s, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity 更多的X，更多的问题：来自X染色体的贡献如何增强女性自身免疫的易感性
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102543
Claudia D Lovell, Montserrat C Anguera
{"title":"More X’s, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity","authors":"Claudia D Lovell,&nbsp;Montserrat C Anguera","doi":"10.1016/j.coi.2025.102543","DOIUrl":"10.1016/j.coi.2025.102543","url":null,"abstract":"<div><div>Many autoimmune diseases exhibit a strong female bias. While sex hormones may influence sex bias in disease, recent studies suggest that the X chromosome itself directly contributes to female-biased susceptibility to autoimmunity. Females with two X chromosomes utilize X Chromosome Inactivation (XCI) to silence gene expression from one X chromosome, equalizing expression between the sexes. The X chromosome is highly enriched with immune-related genes, and recent work indicates that the fidelity of XCI maintenance in lymphocytes from female systemic lupus erythematosus patients is compromised, suggesting that aberrant X-linked gene expression contributes to autoimmune phenotypes. XCI is initiated and maintained by the long noncoding RNA XIST/Xist through its interactions with the inactive X chromosome and numerous interacting proteins, and recent studies also implicate XIST/Xist RNA in driving endosomal Toll-like receptor signaling and XIST/Xist RNA-protein complexes in serving as a source of autoantigens to respectively drive autoimmunity. Here, we will review these three distinct pathways that underscore the significance of X-linked genetics for understanding the origins of the female bias in autoimmune disease.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"93 ","pages":"Article 102543"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Defenders or defectors: mucosal-associated invariant T cells in autoimmune diseases 防御者或叛逃者：自身免疫性疾病中粘膜相关的不变T细胞
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102542
Mitchell Kronenberg , Thomas Riffelmacher
{"title":"Defenders or defectors: mucosal-associated invariant T cells in autoimmune diseases","authors":"Mitchell Kronenberg ,&nbsp;Thomas Riffelmacher","doi":"10.1016/j.coi.2025.102542","DOIUrl":"10.1016/j.coi.2025.102542","url":null,"abstract":"<div><div>Mucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1, a major histocompatibility complex class I–like protein. Activated MAIT cells produce cytokines such as interferon gamma (IFNγ), tumor necrosis factor, and interleukin-17; they traffic to sites of infection and participate in protective responses. They are absent in germ-free mice and are dependent on microbes. MAIT cells not only respond to infections but also have been analyzed in various autoimmune diseases. A trend is that in autoimmune disease, MAIT cells are decreased in the circulation and increased and activated or exhausted in the site of inflammation. Despite a possible pathogenic role, publications show MAIT cells also can function in tissue repair. Mouse autoimmune disease models support the presence of both these MAIT cell functions. The signals driving the balance of inflammatory and tissue repair in MAIT cell responses remain to be fully elucidated.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"93 ","pages":"Article 102542"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Friends close, enemies closer: the complex role of the microbiome in antitumor immunity 朋友更近，敌人更近：微生物群在抗肿瘤免疫中的复杂作用
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102537
Dipyaman Patra , Gagan Dev , Timothy W Hand , Abigail Overacre-Delgoffe
{"title":"Friends close, enemies closer: the complex role of the microbiome in antitumor immunity","authors":"Dipyaman Patra ,&nbsp;Gagan Dev ,&nbsp;Timothy W Hand ,&nbsp;Abigail Overacre-Delgoffe","doi":"10.1016/j.coi.2025.102537","DOIUrl":"10.1016/j.coi.2025.102537","url":null,"abstract":"<div><div>Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"93 ","pages":"Article 102537"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T cell–B cell interactions in human autoimmune diseases T细胞- b细胞在人类自身免疫性疾病中的相互作用
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102539
John M Sowerby, Deepak A Rao
{"title":"T cell–B cell interactions in human autoimmune diseases","authors":"John M Sowerby,&nbsp;Deepak A Rao","doi":"10.1016/j.coi.2025.102539","DOIUrl":"10.1016/j.coi.2025.102539","url":null,"abstract":"<div><div>Activation of autoreactive B cells and production of specific autoantibodies are hallmark features of many autoimmune diseases. B cell differentiation into antibody-secreting cells typically requires help from cognate T cells, which provide both cytokines and cell surface signals in an intricate intercellular interaction. A range of T cells can provide this help to B cells, including T follicular helper cells in follicles of secondary lymphoid organs, as well as T peripheral helper cells, which accumulate within inflamed target tissues in autoimmune diseases. Here, we discuss recent observations about the phenotypes of B cell–helper T cells that accumulate in inflamed tissues and in circulation of patients with autoimmune diseases, the correlations between B cell–helper T cells and B cells in these tissues, and key mediators of productive T cell–B cell interactions, with a focus on mediators that are being targeted therapeutically. Understanding the scope of B cell–helper T cells and their functions will improve our ability to quantify and track pathologic T cell–B cell interactions in human autoimmune diseases and may highlight critical mediators that can be targeted to suppress these interactions therapeutically.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"93 ","pages":"Article 102539"},"PeriodicalIF":6.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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