Immunological Reviews最新文献

Pathological IgE Production in Inborn Errors of Immunity and Beyond 先天性免疫缺陷及其他疾病的病理性IgE产生

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-07-15 DOI: 10.1111/imr.70053

Cindy S. Ma, Peter S. Hsu

引用次数: 0

Innate Immunity and Tertiary Lymphoid Structures 先天免疫和三级淋巴结构

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-07-02 DOI: 10.1111/imr.70052

Ruibo Zhao, Daxing Gao

{"title":"Innate Immunity and Tertiary Lymphoid Structures","authors":"Ruibo Zhao, Daxing Gao","doi":"10.1111/imr.70052","DOIUrl":"https://doi.org/10.1111/imr.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that form in response to chronic inflammation, such as in autoimmune diseases or cancer. Their presence has been increasingly recognized as a significant factor in determining patient prognosis and response to cancer treatments. The formation and development of TLSs are intricately linked to inflammatory cytokines and chemokines, which can be induced by the innate immune system. The innate immune system serves as the body's first line of defense against pathogens by producing cytokines and chemokines upon the detection of foreign invaders. The interplay between innate immunity and TLSs is multifaceted and involves various components and mechanisms. Here, we focus on three key aspects. First, the involvement of specific innate immune cell types in TLS dynamics; second, the role of innate immune receptors in TLS formation; lastly, the contributions of innate immune effectors to TLS formation and maintenance. By examining these interconnected aspects, we can gain a comprehensive understanding of how innate immunity regulates the formation and function of TLSs in the context of chronic inflammation and cancer. This knowledge not only enhances our understanding of immune responses but also holds potential for developing novel therapeutic strategies targeting TLSs in various pathological conditions.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524705","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

The Sunrise of Tertiary Lymphoid Structures in Cancer 癌症中三级淋巴结构的新发现

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-07-01 DOI: 10.1111/imr.70046

Juliette Rochefort, Gilles Marodon, Jean-Luc Teillaud, Marie-Caroline Dieu-Nosjean

{"title":"The Sunrise of Tertiary Lymphoid Structures in Cancer","authors":"Juliette Rochefort, Gilles Marodon, Jean-Luc Teillaud, Marie-Caroline Dieu-Nosjean","doi":"10.1111/imr.70046","DOIUrl":"https://doi.org/10.1111/imr.70046","url":null,"abstract":"<p>First considered as a negative epiphenomenon in autoimmune and inflammatory diseases, with possible deleterious consequences through the production of pathological autoantibodies and antiself T cells, tertiary lymphoid structures (TLS) have gained major scientific and clinical interest in cancer due to their association with better clinical outcomes and improved responses to immunotherapy. Studies have investigated the structure and plasticity of TLS in the context of tumors and the role of the TLS B-cell compartment in contributing to the favorable clinical outcome of cancer patients. Identifying biomarkers that indicate the presence of TLS in tumors in a noninvasive manner could therefore represent a major advance in the diagnosis and treatment decision-making for these patients. Also, the interplay between TLS, tumor cells, and microbiota opens new avenues for deciphering the role of microorganisms in cancer development. Their use as TLS inducers further underlines the need for continued research in this field. Moreover, emerging data have emphasized the critical role of sensory and sympathetic nerves in regulating TLS formation and function. Finally, humanized mice may serve as valuable tools for developing preclinical models to study the role of human TLS in cancer, a much-needed goal. These different topics are discussed in the present review.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524998","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

Burning Down the House: Thymic Repair and Regeneration After Acute Damage 烧毁房子：胸腺修复和再生后的急性损伤

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-28 DOI: 10.1111/imr.70050

Jarrod A. Dudakov, Marcel R. M. van den Brink

{"title":"Burning Down the House: Thymic Repair and Regeneration After Acute Damage","authors":"Jarrod A. Dudakov, Marcel R. M. van den Brink","doi":"10.1111/imr.70050","DOIUrl":"https://doi.org/10.1111/imr.70050","url":null,"abstract":"<div>\u0000 \u0000 <p>The thymus is extremely sensitive to insult but also has a remarkable capacity for endogenous repair. However, even though there is continual thymic involution and regeneration in response to everyday insults like stress and infection, profound thymic damage such as ionizing radiation leads to prolonged T cell lymphopenia for which there is currently no therapeutic treatment. We and others have been focusing in recent years on untangling the cellular and molecular mechanisms underlying endogenous thymic regeneration in the hope of being able to exploit them for clinical benefit. To date, multiple molecular mechanisms have been identified that are centered on several distinct cell axes, including interleukin-22 produced by innate lymphoid cells, BMP4 by endothelial cells, and type 2 cytokines from eosinophils, ILCs, and Tregs. Notably, one of the uniting triggers for these pathways of repair centers on the balance of cell death detection. In this review, we will highlight the current state of play with regard to cellular and molecular pathways of regeneration as well as the mechanisms triggering them. We will also highlight recent work that sheds light on the limitations of thymus repair and speculate as to what will be needed for an effective thymus-boosting therapy.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503237","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

Follicle on the Roof: Tertiary Lymphoid Structures in Central Nervous System Autoimmunity 顶泡：中枢神经系统自身免疫的三级淋巴结构

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-26 DOI: 10.1111/imr.70045

Michelle Zuo, Angela A. Wang, Jennifer L. Gommerman

{"title":"Follicle on the Roof: Tertiary Lymphoid Structures in Central Nervous System Autoimmunity","authors":"Michelle Zuo, Angela A. Wang, Jennifer L. Gommerman","doi":"10.1111/imr.70045","DOIUrl":"https://doi.org/10.1111/imr.70045","url":null,"abstract":"<p>Leptomeningeal tertiary lymphoid structures (TLS) have emerged as a relatively common pathological feature of autoimmune disease, including multiple sclerosis (MS) and particularly in people with progressive and nonremitting MS. These ectopic lymphoid aggregates, observed in the leptomeninges adjacent to so-called “Type 3” sub-pial cortical lesions, are associated with more severe gray matter damage and worse clinical outcomes. Mouse models of MS that recapitulate TLS formation in the central nervous system (CNS) have provided critical insights into the mechanisms driving their development and maintenance. In these models of experimental autoimmune encephalomyelitis (EAE) initiation of TLS is facilitated by Th17 cells, which promote chronic inflammation via cytokines such as IL-17 and GM-CSF. The cell surface expression of lymphotoxin-α and lymphotoxin-β heterotrimers (LTαβ) on lymphocytes, including Th17 cells, elaborates the organization of ectopic lymphoid tissues via LTβR signaling on radio-resistant stromal cells and resident fibroblasts. Ultimately a pro-inflammatory environment characterized by cytokines such as IL-17 and GM-CSF promotes the recruitment of neutrophils which produce proteases and chemokines that sustain a pro-inflammatory milieu. Emerging EAE data suggest that disrupting TLS organization or targeting key pathways involved in their maintenance could represent promising strategies for modulating chronic CNS inflammation in MS. Understanding the cellular and molecular mechanisms regulating TLS dynamics is therefore critical for the development of therapies aimed at halting or reversing nonremitting MS disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482263","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

Is That Lymphocyte Aggregate a Tertiary Lymphoid Organ? Lymphoid Structures in Teleost Fish and the Challenges of Using Mammalian Definitions Across Vertebrate Phylogeny 淋巴细胞聚集体是三级淋巴器官吗？硬骨鱼的淋巴结构和在脊椎动物系统发育中使用哺乳动物定义的挑战

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-25 DOI: 10.1111/imr.70044

Benjamin J Garcia, Irene Salinas

{"title":"Is That Lymphocyte Aggregate a Tertiary Lymphoid Organ? Lymphoid Structures in Teleost Fish and the Challenges of Using Mammalian Definitions Across Vertebrate Phylogeny","authors":"Benjamin J Garcia, Irene Salinas","doi":"10.1111/imr.70044","DOIUrl":"https://doi.org/10.1111/imr.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>Teleost fish are the most diverse of the vertebrate taxa, made up of over 30,000 different species with diverse life histories, unique immune systems and extreme physiological adaptations. Mammalian immunologists coined primary, secondary and tertiary lymphoid organs based on their developmental, anatomical and functional characteristics and such definitions are often “imposed” on other organisms. For decades, teleost fish were thought to lack lymphoid aggregates beyond those found in the primary lymphoid organs of the thymus and the head-kidney or those found in the spleen (a secondary lymphoid organ). However, over the past two decades several laboratories have uncovered the presence of lymphocyte aggregates in several anatomical locations, mostly mucosal barriers, in teleost fish. These aggregates are difficult to classify as secondary or tertiary lymphoid structures based on the current mammal-based framework. This perspective provides an overview of the latest findings in lymphocyte aggregates in teleost fish and their potential function in adaptive immunity. We proposed a revised definition for tertiary lymphoid organs (TLOs) that is relevant across a wider range of vertebrate taxa and where the lack of baseline SLO makes TLO description and functional characterization even harder. Specifically, we propose experimental paradigms where the “ectopic” nature of TLOs could be ascertained in non-model organisms.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472867","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

Deconstructing the Thymic Microenvironment Through Genesis to Senescence 从起源到衰老解构胸腺微环境

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-25 DOI: 10.1111/imr.70048

Michael D'Andrea, Kelin Zhao, Daniel H. D. Gray

引用次数: 0

Cortical Thymic Epithelial Cells: Key Developers of the Code of T-Cell Selection and TCR Repertoire Diversity 胸腺皮质上皮细胞：t细胞选择代码和TCR库多样性的关键开发者

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-25 DOI: 10.1111/imr.70049

Pedro M. Rodrigues, Laura G. Sousa, Nuno L. Alves

{"title":"Cortical Thymic Epithelial Cells: Key Developers of the Code of T-Cell Selection and TCR Repertoire Diversity","authors":"Pedro M. Rodrigues, Laura G. Sousa, Nuno L. Alves","doi":"10.1111/imr.70049","DOIUrl":"https://doi.org/10.1111/imr.70049","url":null,"abstract":"<div>\u0000 \u0000 <p>The thymus is crucial for developing immunocompetent T cells expressing T cell receptors (TCRs) capable of responding to foreign antigens while remaining tolerant to self-components. T cell development involves complex interactions with thymic stromal cells, including thymic epithelial cells (TECs). Particularly, T cell selection relies on the coordinated, yet spatially and temporally distinct functions of rare cortical (cTECs) and medullary (mTECs) subtypes. While cTECs are essential for T cell lineage commitment and positive selection, mTECs play a role in central tolerance by eliminating autoreactive cells and promoting regulatory T cell development. Thus, thymic selection refines the TCR repertoire, promoting immune competence to foreign antigens while ensuring tolerance to self. This review focuses on the instructive role of cTECs in positive selection and CD4/CD8 lineage commitment. It further explores recent discoveries on the molecular mechanisms underlying the generation of selective self-peptide–MHC ligands, which are critical for TCR diversification. We also highlight recent findings on TEC heterogeneity and discuss their potential roles in T cell selection. Understanding TEC diversity and their specialized machinery in generating selective ligands reshapes our view of thymic biology and is key to comprehending their influence on peripheral CD4<sup>+</sup> and CD8<sup>+</sup> T cell functions.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"332 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472869","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

Perivascular Tertiary Lymphoid Structures in Autoimmune Disease 自身免疫性疾病的血管周围三级淋巴结构

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-24 DOI: 10.1111/imr.70047

Jörg J. Goronzy, Cornelia M. Weyand

引用次数: 0

Epitope-Specific Antibodies in Allergic Disease and Clinical Tolerance 过敏性疾病中的表位特异性抗体和临床耐受性

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-06-20 DOI: 10.1111/imr.70042

Orlee Marini-Rapoport, Moumita Bhowmik, Tarun Keswani, Sarita U. Patil

引用次数: 0