Immunological Reviews最新文献

Correction to "The Integrin Receptors: From Discovery to Structure to Medicines". 更正“整合素受体：从发现到结构到药物”。

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-10-01 DOI: 10.1111/imr.70065

引用次数: 0

From Lymphotoxin to Tertiary Lymphoid Structures and Beyond 从淋巴蛋白到三级淋巴结构及以后。

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-29 DOI: 10.1111/imr.70062

Nancy H. Ruddle

{"title":"From Lymphotoxin to Tertiary Lymphoid Structures and Beyond","authors":"Nancy H. Ruddle","doi":"10.1111/imr.70062","DOIUrl":"10.1111/imr.70062","url":null,"abstract":"Lymphoid organ development occurs in ontogeny in the absence of antigenic stimulation; inflammation occurs after some immunological insult. These subjects had originally been considered as separate fields of research. Inflammation is due to inflammatory mediators such as lymphotoxin (LT) and its close relative, tumor necrosis factor (TNF). The two fields converged with the realization that LT is also crucial for secondary lymphoid organ (SLO) development and that it induces chronic lymphoid infiltrates, called tertiary lymphoid organs (TLOs) or tertiary lymphoid structures (TLSs) that are remarkably like SLOs. TLSs, which were initially described in mice transgenic for the rat insulin promoter driving LT (RIPLT mice), occur in chronic inflammation in autoimmune diseases, atherosclerosis, graft rejection, microbial infection, aging, and cancer. The thesis presented here is that understanding SLO development, structure, and function is key to understanding TLSs. Key discoveries are presented which include the observations that LT's two forms, LTα3 and LTα1β2, signal through different receptors that induce both SLOs and TLSs. Similarities and differences between TLSs and SLOs are presented. Prospects for their inhibition in autoimmune diseases where they are detrimental, and induction in cancer, where they are beneficial, are presented. Challenges and future directions are discussed.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"335 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184374","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

Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers 跨器官的三级淋巴结构：背景、组成和临床杠杆

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-25 DOI: 10.1111/imr.70063

Stephane M. Guillaume, Cristian G. Beccaria, Matteo Iannacone, Michelle A. Linterman

{"title":"Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers","authors":"Stephane M. Guillaume, Cristian G. Beccaria, Matteo Iannacone, Michelle A. Linterman","doi":"10.1111/imr.70063","DOIUrl":"https://doi.org/10.1111/imr.70063","url":null,"abstract":"Tertiary lymphoid structures (TLSs) arise in non-lymphoid tissues in response to persistent antigen stimulation and chronic inflammation. Spanning organs from lung and liver to meninges, skin, and beyond, TLSs range from loose aggregates of immune cells to fully mature structures containing functional germinal centers (GC). In this review, we provide a comprehensive overview of TLS formation, architecture, and function across diverse tissues, highlighting both shared features and tissue-specific adaptations. We then explore the clinical relevance of TLS in infections, autoimmunity, cancer, and allergy, emphasizing their dual roles in mediating protective immunity and driving pathology. Finally, we discuss emerging technologies that are transforming our ability to dissect TLSs at high resolution (including spatial multi-omics, advanced imaging, and digital pathology), enabling mechanism-guided strategies to modulate TLSs therapeutically. Framing TLSs through the lens of maturation and tissue context provides a foundation for interpreting their clinical associations and for enhancing or dismantling these niches according to need.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"335 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135669","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

Human Atypical B Cells. An Overview 人非典型B细胞。概述。

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-19 DOI: 10.1111/imr.70058

Iñaki Sanz

引用次数: 0

Extrafollicular and Other Non-Germinal Center B Cell Responses: An Evolutionary Perspective 滤泡外和其他非生发中心B细胞反应：进化的观点

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-12 DOI: 10.1111/imr.70060

Emily M. Flowers, Emily R. Siniscalco, Stephanie C. Eisenbarth

{"title":"Extrafollicular and Other Non-Germinal Center B Cell Responses: An Evolutionary Perspective","authors":"Emily M. Flowers, Emily R. Siniscalco, Stephanie C. Eisenbarth","doi":"10.1111/imr.70060","DOIUrl":"https://doi.org/10.1111/imr.70060","url":null,"abstract":"<div>\u0000 \u0000 Classic models of humoral immunity focus on the role of germinal centers (GCs) in producing high affinity, class switched protective antibodies. However, antibodies can also be produced through a diverse range of GC-independent pathways. Such pathways are often labeled “extrafollicular”, even when the localization of individual responses remains unknown, but in this review, we group them together under the broad umbrella of “nonGC responses”. Experiments in mammals show that nonGC responses provide important humoral protection against infections and complement the eventual GC-derived antibody response. In this review, we explore the immunological foundations of nonGC and GC responses through an evolutionary lens and investigate the mechanisms of humoral immunity throughout vertebrate evolution. In animals that predate the evolution of GCs as they appear in mammals, B cell responses still occur at organized sites and with features also seen in mammals, including adjacent T cell and B cell regions, sites for antigen deposit, and B cell proliferation and mutation. Here we review the commonalities in nonGC responses across multiple genera, before and after the emergence of GCs. This comparison helps frame current efforts to mechanistically understand pathways for nonGC responses and the relative roles of GC- and nonGC-derived antibodies in humoral immunity.\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"334 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038267","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

Tertiary Lymphoid Organs at the Center Stage of Skin's Humoral Immunity 第三淋巴器官在皮肤体液免疫的中心阶段

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-05 DOI: 10.1111/imr.70061

Inta Gribonika

{"title":"Tertiary Lymphoid Organs at the Center Stage of Skin's Humoral Immunity","authors":"Inta Gribonika","doi":"10.1111/imr.70061","DOIUrl":"https://doi.org/10.1111/imr.70061","url":null,"abstract":"The skin is the outermost organ that serves as the host's live, microbiota-inhabited physical border, evolved to cope with continuous confrontation by a wide variety of environmental elements. This dynamic borderline is prone to injury and damage. Therefore, to deliver on the critical demands for protection, skin is tightly associated with innate and adaptive defense mechanisms that ensure homeostatic tissue barrier integrity. We recently described the skin's ability to form its own autonomous and protective immune response independently of known professional organs. Cutaneous immunocompetence was achieved through the formation of dermal tertiary lymphoid organs (TLOs) that provide protective humoral activity similar to the classical germinal center reaction in the lymph node. This response was mediated by cutaneous microbiota uncoupled from inflammatory signals and positioned within the healthy skin. Our findings illustrate the power of non-inflammatory host-microbiota interaction and open a door for reevaluation of topical disease development and progression. A detailed understanding of highly coordinated tissue-specific determinants that facilitate local antibody response may provide innovative solutions in skin health care and therapies. In this review, I elaborate on our findings and argue for TLO's importance in the host's immune arsenal, which is at the very center of skin's humoral immunity.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"334 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998801","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

Tissue-Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells 促进体液免疫的组织常驻T细胞：从T滤泡辅助细胞的阴影中出现

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-09-01 DOI: 10.1111/imr.70056

Shuting Chen, Joseph Craft

{"title":"Tissue-Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells","authors":"Shuting Chen, Joseph Craft","doi":"10.1111/imr.70056","DOIUrl":"https://doi.org/10.1111/imr.70056","url":null,"abstract":"Humoral immune responses are critical for protection against immune challenge by pathogens and transformed cells, while dysregulated antibody production is a hallmark of autoimmune diseases. T follicular helper (Tfh) cells are central to the development of humoral immunity, regulating B-cell maturation, including immunoglobulin class switch recombination and somatic hypermutation, and development of memory B and antibody-producing plasma cells. These events occur as B cells migrate to and differentiate within B cell follicles of secondary lymphoid organs, with this classical program of follicular B cell maturation providing systemic immune protection. Local humoral responses are also necessary for organismal defense against immune challenge. Accordingly, T-dependent B-cell help occurs outside of B-cell follicles, including in non-lymphoid tissues such as the lung, central nervous system, joints, and kidneys. The phenotype and function of T cells that provide humoral protection against pathogens and tumors and conversely promote autoimmunity at the tissue level both overlap with and are distinct from those of canonical Tfh cells. Here, we summarize current knowledge of these tissue T-B helper cells, focusing on their differentiation and function in infection, cancer, and autoimmunity.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"334 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927502","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

Role of Fibroblast-Immune Crosstalk in Kidney, Lung, and Skin Tertiary Lymphoid Structures 成纤维细胞免疫串扰在肾、肺和皮肤三级淋巴组织中的作用

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-08-29 DOI: 10.1111/imr.70059

Amy Cross, Jennifer Shelley, Rebecca Newman, Jessica Strid, Alice E. Denton

{"title":"Role of Fibroblast-Immune Crosstalk in Kidney, Lung, and Skin Tertiary Lymphoid Structures","authors":"Amy Cross, Jennifer Shelley, Rebecca Newman, Jessica Strid, Alice E. Denton","doi":"10.1111/imr.70059","DOIUrl":"https://doi.org/10.1111/imr.70059","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are organized aggregates of lymphocytes, myeloid cells, and stromal cells that form at sites of inflammation, providing adaptive immune responses outside of secondary lymphoid organs (SLOs). Found in various pathological conditions—including chronic infections, cancer, organ transplantation, autoimmune diseases, and allergy—the presence of TLSs is linked to potentiation of local immunity. TLSs can be beneficial or detrimental, depending on context, and have been implicated as prognostic for disease severity and therapy response. Architecturally, TLSs resemble SLOs with distinct T and B cell areas supported by fibroblasts that secrete chemokines and cytokines that support immune cells. These structures must be created de novo in non-lymphoid tissues; thus, the steps for TLS formation mimic, but do not completely copy, those of SLO formation. The accumulation of immune cells in tissues in inflammatory settings can initiate remodeling of tissue fibroblasts, leading to TLS formation; this process is common across tissues, although there are tissue- and disease-specific pathways that impact TLS formation in certain contexts. This review will explore the immune-stromal crosstalk in kidney, lung, and skin TLSs across a range of disease settings, highlighting shared as well as tissue-specific mechanisms for TLS formation.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"334 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918817","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

IgE in Allergic Diseases 过敏性疾病中的IgE

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-08-27 DOI: 10.1111/imr.70057

Dana Greene, Jamie Moore Fried, Julie Wang

引用次数: 0

Tertiary Lymphoid Structures in Tuberculosis: Persistence, Protection, and Pathology 结核病的三级淋巴结构：持续性、保护和病理

IF 8.3 2区医学

Immunological Reviews Pub Date : 2025-08-15 DOI: 10.1111/imr.70055

Tiphaine M. N. Camarasa, Lorenzo Iseppi, David Schreiner, Carolyn G. King

{"title":"Tertiary Lymphoid Structures in Tuberculosis: Persistence, Protection, and Pathology","authors":"Tiphaine M. N. Camarasa, Lorenzo Iseppi, David Schreiner, Carolyn G. King","doi":"10.1111/imr.70055","DOIUrl":"https://doi.org/10.1111/imr.70055","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health burden responsible for over a million deaths each year. A deeper understanding of the mechanisms that balance protective immunity and immunopathology is essential for developing more effective therapeutics. This review focuses on the dynamic interplay between CD4+ T cells and B cells in the lung, with an emphasis on their interactions in tertiary lymphoid structures (TLS). TLS are immune cell aggregates that arise in inflamed, nonlymphoid tissues, range from loosely to highly organized clusters, and serve as localized hubs for immune cell interaction, activation, and diversification. Drawing on insights from other disease contexts, including infections, cancer, and chronic inflammatory conditions, we examine the molecular signals and cellular interactions involved in TLS formation, maintenance, and function during Mtb infection. Additionally, we explore the anatomical and functional integration of TLS with the lymphatic and vascular systems, and how this spatial organization may influence bacterial persistence and dissemination. Clarifying the functional role of TLS in TB—whether they support protective immunity, contribute to lung pathology, or both—could inform novel approaches to modulate local immune responses and improve TB disease outcomes.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"333 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843510","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