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Advances in genetic–immunological targeted therapies for psoriasis 银屑病遗传免疫靶向治疗研究进展
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-30 DOI: 10.1016/j.coi.2025.102559
Qi Zhen , Yirui Wang , Zhuo Li , Liangdan Sun
{"title":"Advances in genetic–immunological targeted therapies for psoriasis","authors":"Qi Zhen ,&nbsp;Yirui Wang ,&nbsp;Zhuo Li ,&nbsp;Liangdan Sun","doi":"10.1016/j.coi.2025.102559","DOIUrl":"10.1016/j.coi.2025.102559","url":null,"abstract":"<div><div>Psoriasis is a common chronic immune-mediated inflammatory skin disease, with its pathogenesis involving genetic susceptibility, abnormal immune responses, and environmental factors. In recent years, targeted immunotherapy has become a prominent treatment approach. Various drugs targeting cytokines, such as interleukin-17, interleukin-23, and tumor necrosis factor-α, have been introduced, effectively alleviating symptoms. However, due to the complex immunopathogenesis of psoriasis and individual patient differences, single-target drugs may not consistently provide comprehensive treatment effects. Therefore, this article suggests that future research should prioritize multitarget combination therapies to enhance efficacy and reduce resistance. Personalized treatment strategies, based on patients’ genetic, immune, and clinical characteristics, should be developed. Investigating new immunomodulatory mechanisms and drugs, as well as combination therapies that integrate targeted drugs with phototherapy or cellular therapy, is also crucial. Additionally, exploring long-term efficacy and resistance mechanisms will help improve treatment outcomes, with the goal of transforming psoriasis treatment.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102559"},"PeriodicalIF":6.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891415","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
Autoimmunity in inflammatory bowel disease: a holobiont perspective 炎症性肠病的自身免疫：全息视角
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-18 DOI: 10.1016/j.coi.2025.102557
Henry Taylor , Holm H Uhlig , Fiona Powrie
{"title":"Autoimmunity in inflammatory bowel disease: a holobiont perspective","authors":"Henry Taylor ,&nbsp;Holm H Uhlig ,&nbsp;Fiona Powrie","doi":"10.1016/j.coi.2025.102557","DOIUrl":"10.1016/j.coi.2025.102557","url":null,"abstract":"<div><div>Adaptive immunity towards self-antigens (autoimmunity) and intestinal commensal microbiota is a key feature of inflammatory bowel disease (IBD). Considering mucosal adaptive immunity from a holobiont perspective, where the host and its microbiome form a single physiological unit, emphasises the challenge of avoiding damaging responses to self-antigen and symbiotic microbial communities in the gut while protecting against potential pathogens. Intestinal tolerance mechanisms prevent maladaptive T and B cell responses to microbial, environmental, and self-antigens, which drive inflammation. We discuss the spectrum of antimicrobial and autoantibody responses and highlight mechanisms by which common IBD-associated adaptive immune responses contribute to disease.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102557"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844393","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
Drivers and shapers of macrophages specification in the developing brain 脑发育过程中巨噬细胞规范的驱动者和塑造者
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-15 DOI: 10.1016/j.coi.2025.102558
Simone Brioschi , Claudia Z Han , Marco Colonna
{"title":"Drivers and shapers of macrophages specification in the developing brain","authors":"Simone Brioschi ,&nbsp;Claudia Z Han ,&nbsp;Marco Colonna","doi":"10.1016/j.coi.2025.102558","DOIUrl":"10.1016/j.coi.2025.102558","url":null,"abstract":"<div><div>The brain harbors two major macrophage populations: microglia reside within the brain parenchyma, while border-associated macrophages (BAMs) are situated at central nervous system (CNS) interfaces. BAMs can be further classified into distinct subsets based on their localization: perivascular macrophages surround blood vessels, meningeal macrophages reside in the leptomeninges, dura macrophages in the dura mater, and choroid plexus macrophages are confined to the choroid plexus. The environmental factors and molecular mechanisms driving the specification of these macrophage populations are still being elucidated. Deciphering the communication pathways between CNS macrophages and their tissue niches during development, homeostasis, and pathologic conditions offers significant potential for treating a wide range of brain disorders, from neurodevelopmental and neuroinflammatory diseases to neurovascular and neurodegenerative conditions. With this short review, we will address the current understanding and knowledge gaps in the field, as well as the future directions for the upcoming years.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102558"},"PeriodicalIF":6.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830294","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
Autoimmune-related adverse events induced by immune checkpoint inhibitors 免疫检查点抑制剂诱导的自身免疫相关不良事件
IF 6.6 2区 医学
Current Opinion in Immunology Pub Date : 2025-04-11 DOI: 10.1016/j.coi.2025.102556
Yuanqiang Sun , Ziyang Zhang , Ke Jia , Hong Liu , Furen Zhang
{"title":"Autoimmune-related adverse events induced by immune checkpoint inhibitors","authors":"Yuanqiang Sun ,&nbsp;Ziyang Zhang ,&nbsp;Ke Jia ,&nbsp;Hong Liu ,&nbsp;Furen Zhang","doi":"10.1016/j.coi.2025.102556","DOIUrl":"10.1016/j.coi.2025.102556","url":null,"abstract":"<div><div>Targeted immunotherapies, particularly immune checkpoint inhibitors (ICIs), have transformed cancer treatment by significantly improving patient response and survival rates. However, ICIs could disrupt self-tolerance, inducing the development of immune-related adverse events (irAEs). Most irAEs are classified as autoimmune conditions mediated by ICI-activated CD8+ cytotoxic T cells or activated B cells producing pathogenic autoantibodies. These irAEs phenotypically resemble spontaneous autoimmune disease and lead to considerable morbidity, health care costs, and compromised treatment efficacy. With the widespread use and new emergence of ICIs, the spectrum of ICI-induced irAEs has become increasingly extensive and complex. Concurrently, research in this field is advancing rapidly, a review summarizing the latest progress on irAEs is timely and essential. In this review, we highlight numerous recent research advances, covering the epidemiology, immune mechanisms, and diverse manifestations of irAEs, with a particular focus on organ-specific autoimmunity. We also discuss current strategies, challenges, and future directions for the prevention and therapeutic management of these adverse events.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102556"},"PeriodicalIF":6.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815666","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
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
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