Immunological Reviews最新文献

Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions 分子洞察mr1介导的T细胞免疫：经验教训和未解决的问题

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-05-07 DOI: 10.1111/imr.70033

Wael Awad, Mohamed R. Abdelaal, Victoria Letoga, James McCluskey, Jamie Rossjohn

{"title":"Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions","authors":"Wael Awad, Mohamed R. Abdelaal, Victoria Letoga, James McCluskey, Jamie Rossjohn","doi":"10.1111/imr.70033","DOIUrl":"https://doi.org/10.1111/imr.70033","url":null,"abstract":"<p>The major histocompatibility complex class-I related protein, MR1, is an evolutionarily conserved antigen presenting molecule that binds and displays organic metabolites to T cells, including mucosal associated invariant T (MAIT) cells and diverse MR1-restricted T cells (MR1T). Structural studies have elucidated how MR1 can accommodate a range of chemical scaffolds that arise from foreign, synthetic, and self-metabolites, although the full spectrum of metabolites that MR1 presents remains unclear. Presently, MAIT and MR1T cell recognition of MR1-antigen complexes represents a new immune recognition paradigm and is emerging as a critical player in protective immunity, aberrant immunity, tumor immunity, and tissue repair. Moreover, the limited allelic variation of MR1 makes it an attractive therapeutic target. This review will address the unique features and capability of the MR1 molecule to display several classes of small molecules for T cell surveillance. We will also address the molecular basis underlying MAIT and MR1T TCR recognition of MR1-binding ligands.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919590","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 the Regulation of Adaptive Immune Responses IgE在适应性免疫反应中的调节作用

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-05-05 DOI: 10.1111/imr.70030

Paul Engeroff, Monique Vogel

{"title":"IgE in the Regulation of Adaptive Immune Responses","authors":"Paul Engeroff, Monique Vogel","doi":"10.1111/imr.70030","DOIUrl":"https://doi.org/10.1111/imr.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunoglobulin E (IgE) plays a dual role in the immune system, providing protection against pathogens while also mediating pathological hypersensitivity reactions. Its function is mainly studied in the context of immediate inflammatory responses, where IgE-sensitized effector cells, such as mast cells and basophils, are triggered by a cross-linking antigen. An often-overlooked feature of IgE biology is its strong ability to boost secondary adaptive immune responses, thus acting as a physiological adjuvant. The regulation of these responses is influenced by various factors, including the primary Ig structure, post-translational modifications such as glycosylations, structural properties of the antigens, and the interaction of IgE with immune receptors. Interestingly, IgE not only generates antigen-specific immune responses, but also IgE-specific autoimmune responses. Natural IgG anti-IgE autoantibodies circulate at surprisingly high levels, even in healthy individuals, contributing to the regulation of IgE serum levels and its interaction with receptors. Understanding these emerging concepts, beyond a singular focus on initial IgE production and immediate effector cell activation, could contribute to a better understanding of the immunological functions of IgE. In this review, we aim to provide an overview of current knowledge on IgE immunogenicity. Many open questions remain on the negative and positive feedback mechanisms by which IgE regulates the adaptive immune response, and we hope to inspire future research into the mechanisms underlying IgE-regulated immune responses and their potential implications for therapeutic strategies in hypersensitivity diseases.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904907","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

Glycobiology of IgE IgE的糖生物学

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-05-05 DOI: 10.1111/imr.70032

Aron Gyorgypal, Sayantan Banerjee, Michelle E. Conroy, Robert M. Anthony

{"title":"Glycobiology of IgE","authors":"Aron Gyorgypal, Sayantan Banerjee, Michelle E. Conroy, Robert M. Anthony","doi":"10.1111/imr.70032","DOIUrl":"https://doi.org/10.1111/imr.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Antibodies play a vital role in the immune system, with distinct isotypes having unique tropisms and performing specialized functions. Of these isotypes, IgE is the least abundant in circulation yet plays a critical role in defense against parasitic infection and allergic reactions. IgE is also heavily N-linked glycosylated, a posttranslational modification that influences receptor interactions of effector responses. The importance of glycosylation on IgG function is well established, and the roles of IgE glycans are emerging. This review examines the relationship between IgE glycosylation and its biological function. IgE glycosylation, specifically the oligomannosidic glycan, is necessary for IgE binding to its high-affinity receptor FcεRI on mast cells and basophils. Recent evidence suggests that terminal sialic acid residues on complex biantennary glycans significantly enhance IgE's allergic potential, with sialylation of IgE demonstrating reduced capacity to trigger degranulation and anaphylaxis. Glycosylation also influences IgE's interaction with its low-affinity receptor FcεRII/CD23, affecting serum clearance and antigen presentation. Beyond allergy, this review also covers IgE's impacts on its roles in autoimmunity, parasite defense, and protection against venoms. Current therapeutic approaches targeting IgE include monoclonal antibodies like omalizumab, with emerging therapeutics looking to target systemic IgE production mechanisms also covered. Although the understanding of IgG glycosylation is known, there is much to uncover in terms of IgE glycosylation, which may open new avenues for developing more precise interventions that modulate its effector functions.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904906","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

Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition 对IgE受体相互作用和破坏性抑制的结构和功能见解

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-30 DOI: 10.1111/imr.70031

Alexander Eggel, Theodore S. Jardetzky

{"title":"Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition","authors":"Alexander Eggel, Theodore S. Jardetzky","doi":"10.1111/imr.70031","DOIUrl":"https://doi.org/10.1111/imr.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunoglobulin E (IgE) plays a critical role in host defense against parasites and venoms but is also best known for its central involvement in allergic reactions. Through interactions with its high- and low-affinity receptors, FcεRI and CD23, respectively, IgE sensitizes mast cells and basophils, drives antigen presentation, regulates antibody production, and overall amplifies type 2 immunity. The unique conformational flexibility of IgE, particularly within its Cε2-Cε4 domains of the Fc-region, has emerged as a key determinant of receptor specificity and function. Structural studies have revealed that IgE adopts distinct open and closed conformations that selectively enable FcεRI or CD23 binding. These insights have reshaped our understanding of receptor engagement and laid the foundation for therapeutic targeting approaches of IgE:receptor interactions to treat allergies. Initial anti-IgE biologics, such as omalizumab, were developed to neutralize free IgE in circulation and prevent receptor binding. While clinically successful, this approach has limitations, such as the inefficient targeting of receptor-bound IgE and the requirement for prolonged and frequent injections to achieve therapeutic benefit. Recent advances have led to the development of a new class of anti-IgE molecules termed “disruptive” IgE inhibitors that actively disassemble preformed IgE:FcεRI complexes. By exploiting conformational dynamics, creating steric interference, or allosteric mechanisms, these molecules, in addition to their neutralizing capacity, enable rapid active desensitization of allergic effector cells. In this review, we highlight how an improved structural and mechanistic understanding of IgE and its receptors has guided the design of such next-generation anti-IgE molecules. Such multifunctional biologics might offer faster onset, broader activity, and potential use in acute allergic situations, setting the stage for a new era in IgE-targeted therapy.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893022","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

Mucins and Their Roles in Asthma 粘蛋白及其在哮喘中的作用

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-30 DOI: 10.1111/imr.70034

Qihua Ye, Gilda Opoku, Marika Orlov, Ana M. Jaramillo, Fernando Holguin, Eszter K. Vladar, William J. Janssen, Christopher M. Evans

引用次数: 0

Maternal IgE Influence on Fetal and Infant Health 母体IgE对胎儿和婴儿健康的影响

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-25 DOI: 10.1111/imr.70029

Jozef Balla, Abhay P. S. Rathore, Ashley L. St. John

{"title":"Maternal IgE Influence on Fetal and Infant Health","authors":"Jozef Balla, Abhay P. S. Rathore, Ashley L. St. John","doi":"10.1111/imr.70029","DOIUrl":"https://doi.org/10.1111/imr.70029","url":null,"abstract":"<p>Immunoglobulin E (IgE) is the most recently discovered and evolved mammalian antibody type, best known for interacting with mast cells (MCs) as immune effectors. IgE-mediated antigen sensing by MC provides protection from parasites, venomous animals, bacteria, and other insults to barrier tissues exposed to the environment. IgE and MCs act as inflammation amplifiers and immune response adjuvants. Thus, IgE production and memory formation are greatly constrained and require specific licensing. Failure of regulation gives rise to allergic disease, one of the top causes of chronic illness. Increasing evidence suggests allergy development often starts early in life, including prenatally, with maternal influence being central in shaping the offspring's immune system. Although IgE often exists before birth, an endogenous source of IgE-producing B cells has not been identified. This review discusses the mechanisms of maternal IgE transfer into the offspring, its interactions with offspring MCs and antigen-presenting cells, and the consequences for allergic inflammation and allergen sensitization development. We discuss the multifaceted effects of pre-existing IgG, IgE, and their glycosylation on maternal IgE transfer and functionality in the progeny. Understanding the IgE-mediated mechanisms predisposing for early life allergy development may allow their targeting with existing therapeutics and guide the development of new ones.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875574","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

Thymic Mimetic Cells: Evolutionarily Ancient Mirrors of the Periphery 胸腺模拟细胞：进化上古老的外周镜像

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-17 DOI: 10.1111/imr.70028

Brooke D. Huisman, Chong Zuo, Diane Mathis

{"title":"Thymic Mimetic Cells: Evolutionarily Ancient Mirrors of the Periphery","authors":"Brooke D. Huisman, Chong Zuo, Diane Mathis","doi":"10.1111/imr.70028","DOIUrl":"https://doi.org/10.1111/imr.70028","url":null,"abstract":"<p>Thymic mimetic cells are hybrids of medullary thymic epithelial cells and diverse peripheral cell types. They are important for the imposition of self-tolerance and perform other functions similar to those of their peripheral counterparts. Following early histological observations of “misplaced” stromal cells in thymi from multiple species, mimetic cells were first molecularly investigated in mice. Recent studies have characterized mimetic cells in humans and zebrafish with high-resolution. Many mimetic cell types are conserved across species, although specialized subtypes as well as variable frequencies and levels of specialization are also apparent. Features of the human mimetic cell repertoire, such as the expanded nature of muscle mimetic cells with potential implications in myasthenia gravis and the similarity of tuft mimetic cells and thymic carcinomas, hint at their relevance in human disease. Here we review what is known about mimetic cells across diverse organisms. We discuss potential pressures shaping the composition of the mimetic cell repertoire within and across species, and highlight potential therapeutic applications in human disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846056","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

Pathobiology and Regulation of Eosinophils, Mast Cells, and Basophils in Allergic Asthma 过敏性哮喘中嗜酸性粒细胞、肥大细胞和嗜碱性粒细胞的病理生物学和调控

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-16 DOI: 10.1111/imr.70018

Christiane E. Whetstone, Rand Amer, Samarah Maqbool, Tooba Javed, Gail M. Gauvreau

{"title":"Pathobiology and Regulation of Eosinophils, Mast Cells, and Basophils in Allergic Asthma","authors":"Christiane E. Whetstone, Rand Amer, Samarah Maqbool, Tooba Javed, Gail M. Gauvreau","doi":"10.1111/imr.70018","DOIUrl":"https://doi.org/10.1111/imr.70018","url":null,"abstract":"<p>Eosinophilia is a hallmark of allergic disorders, including asthma, allergic rhinitis, and atopic dermatitis. The onset and maintenance of allergic inflammation in atopic adults involves the activation of selective hemopoietic processes and the migration of mature and immature eosinophils to allergic tissue, where these cells release mediators of inflammation that participate in the regulation of inflammation. Eosinophils function in close cooperation with basophils and mast cells in allergic tissue, where crosstalk between these central effector cells regulates the inflammatory process. This chapter will review the cellular events leading to the accumulation of eosinophils and their progenitors in the airways in allergic asthma, with a particular focus on models of allergen-induced allergic inflammation. Inhaled allergen challenges in allergic asthmatics have advanced understanding of the pathogenesis of allergen exposure leading to early and late asthmatic responses and the associated airway hyperresponsiveness and type 2 airway inflammation. This chapter will also discuss the mechanisms of commonly used asthma therapies on allergen-induced eosinophilia and compare the effects of novel therapies targeting specific immune pathways for a better understanding of how to regulate airway eosinophil levels in patients with asthma.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836181","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

Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation 小鼠肥大细胞分化的转录调控及人肺肥大细胞在气道炎症中的作用

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-11 DOI: 10.1111/imr.70026

Junfeng Gao, Dianzheng Zhao, Hamid Reza Nouri, Hong Wei Chu, Hua Huang

引用次数: 0

Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ IL-12和IFNγ协同调节滤泡外B细胞反应

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-04-11 DOI: 10.1111/imr.70027

Rebecca A. Elsner, Mark J. Shlomchik

{"title":"Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ","authors":"Rebecca A. Elsner, Mark J. Shlomchik","doi":"10.1111/imr.70027","DOIUrl":"https://doi.org/10.1111/imr.70027","url":null,"abstract":"<p>Upon activation, B cells undergo either the germinal center (GC) or extrafollicular (EF) response. While GC are known to generate high-affinity memory B cells and long-lived plasma cells, the role of the EF response is less well understood. Initially, it was thought to be limited to that of a source of fast but lower-quality antibodies until the GC can form. However, recent evidence strongly supports the EF response as an important component of the humoral response to infection. EF responses are now also recognized as a source of pathogenic B cells in autoimmune diseases. The EF response itself is dynamic and regulated by pathways that are only recently being uncovered. We have identified that the cytokine IL-12 acts as a molecular switch, enhancing the EF response and suppressing GC through multiple mechanisms. These include direct effects on both B cells themselves and the coordinated differentiation of helper CD4 T cells. Here, we explore this pathway in relation to other recent advancements in our understanding of the EF response's role and highlight areas for future research. A better understanding of how the EF response forms and is regulated is essential for advancing treatments for many disease states.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818535","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