Immunological Reviews最新文献

{"title":"Maternal IgE Influence on Fetal and Infant Health","authors":"Jozef Balla,&nbsp;Abhay P. S. Rathore,&nbsp;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}

{"title":"Thymic Mimetic Cells: Evolutionarily Ancient Mirrors of the Periphery","authors":"Brooke D. Huisman,&nbsp;Chong Zuo,&nbsp;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}

{"title":"Pathobiology and Regulation of Eosinophils, Mast Cells, and Basophils in Allergic Asthma","authors":"Christiane E. Whetstone,&nbsp;Rand Amer,&nbsp;Samarah Maqbool,&nbsp;Tooba Javed,&nbsp;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}

{"title":"Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation","authors":"Junfeng Gao,&nbsp;Dianzheng Zhao,&nbsp;Hamid Reza Nouri,&nbsp;Hong Wei Chu,&nbsp;Hua Huang","doi":"10.1111/imr.70026","DOIUrl":"https://doi.org/10.1111/imr.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Mast cells (MCs) play a critical role in allergic inflammation, anaphylaxis, and chronic inflammatory diseases such as asthma, COPD, and osteoarthritis. Dysregulated MC activation can lead to MC activation syndrome (MACS), which is observed in patients with long COVID. MCs express the high-affinity receptor for IgE and, upon activation, release mediators and cytokines that trigger anaphylactic shock and promote allergic inflammation. They also interact with epithelial and nerve cells, which are crucial in forming a complex network of cell–cell and gene–gene interactions driving chronic inflammation that can confer resistance to treatment. In this review, in the context of the literature, we focus on experiments conducted in our laboratory investigating how transcription factors and enhancers regulate genes critical in mouse MC differentiation and function related to human lung inflammation.</p>\u0000 </div>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818536","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}

{"title":"Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ","authors":"Rebecca A. Elsner,&nbsp;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}

{"title":"Touching a Nerve: Neuroimmune Interactions in Asthma","authors":"James M. Kornfield,&nbsp;Hoyt Bright,&nbsp;Matthew G. Drake","doi":"10.1111/imr.70025","DOIUrl":"https://doi.org/10.1111/imr.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Asthma is an inflammatory airway disease characterized by excessive bronchoconstriction and airway hyperresponsiveness. Airway nerves play a crucial role in regulating these processes. In asthma, interactions between inflammatory cells and nerves result in nerve dysfunction, which worsens airway function. This review discusses new insights regarding the role of airway nerves in healthy lungs and examines how communication between nerves and leukocytes, including eosinophils, mast cells, dendritic cells, and innate lymphoid cells, contributes to nerve dysfunction and the worsening of airway disease. Clinical implications and therapeutic opportunities presented by neuroimmune interactions are also addressed.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778410","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}

{"title":"The Structural Biology of T-Cell Antigen Detection at Close Contacts","authors":"Yuan Lui,&nbsp;João Ferreira Fernandes,&nbsp;Mai T. Vuong,&nbsp;Sumana Sharma,&nbsp;Ana Mafalda Santos,&nbsp;Simon J. Davis","doi":"10.1111/imr.70014","DOIUrl":"https://doi.org/10.1111/imr.70014","url":null,"abstract":"<p>T cells physically interrogate their targets using tiny membrane protrusions called microvilli, forming junctions ~400 nm in diameter and ~ 15 nm deep, referred to as “close contacts”. These contacts, which are stabilized by the binding of the small adhesion protein CD2 to its ligand, CD58 and locally exclude large proteins such as the phosphatase CD45, are the sites of antigen recognition by the T-cell receptor (TCR) and very early signaling by T cells. With our collaborators, we have characterized the molecular structures of several of the key proteins mediating these early events: i.e., CD2 and its ligands, CD45, the αβ- and γδ-TCRs, and the accessory proteins CD28, CTLA-4, and PD-1. Here, we review our structural work and the insights it offers into the early events underpinning T-cell responsiveness that take place in the confined space of the close contact. We reflect on the crucial roles that the structural organization and dimensions of these proteins are likely to have in determining the sequence of events leading to antigen recognition at close contacts and consider the general implications of the structural work for explanations of how immune receptor signaling is initiated.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769970","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}

{"title":"A Brief Molecular History of Vγ9Vδ2 TCR-Mediated Phosphoantigen Sensing","authors":"Fiyaz Mohammed,&nbsp;Carrie R. Willcox,&nbsp;Benjamin E. Willcox","doi":"10.1111/imr.70023","DOIUrl":"https://doi.org/10.1111/imr.70023","url":null,"abstract":"<p>Vγ9Vδ2 T-cells are universally present in humans and represent one of the most prevalent TCR reactivities, evolutionarily conserved across diverse mammalian species. They are an innate-like subset featuring a semi-invariant TCR repertoire that drives their well-recognized reactivity to small, non-peptidic phosphoantigens (pAg). Crucially, they can distinguish between highly immunostimulatory microbially derived pAg and much less potent host-derived pAg, with the former effectively acting as a pathogen associated molecular pattern (PAMP) and the Vγ9Vδ2 TCR as a surrogate pattern recognition receptor (PRR). Ample evidence supports important Vγ9Vδ2-mediated contributions to immunity against diverse pathogenic bacteria and parasites, mediated by their potent effector and immunoregulatory functions. The molecular basis of the pAg sensing mechanism underpinning such responses has, however, remained highly mysterious. Despite this, past studies have established that pAg sensing is MHC-independent, extremely fast, exquisitely pAg-sensitive, and dependent upon target cell expression of key BTN-family molecules, notably BTN3A and BTN2A1. Here we contextualize these findings and several recent studies addressing pAg sensing. We integrate these into a single unified theory of pAg sensing interpretable from different perspectives, both intracellular and extracellular, biophysical, and topological. We prioritize critical questions to address in the context of this proposed model. Finally, we suggest the model will provide a molecular template for antigen recognition by other related γδ T-cell subsets.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770147","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}

{"title":"IgE-Mediated Activation of Mast Cells and Basophils in Health and Disease","authors":"Nicolas Charles,&nbsp;Ulrich Blank","doi":"10.1111/imr.70024","DOIUrl":"https://doi.org/10.1111/imr.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Type 2-mediated immune responses protect the body against environmental threats at barrier surfaces, such as large parasites and environmental toxins, and facilitate the repair of inflammatory tissue damage. However, maladaptive responses to typically nonpathogenic substances, commonly known as allergens, can lead to the development of allergic diseases. Type 2 immunity involves a series of prototype TH2 cytokines (IL-4, IL-5, IL-13) and alarmins (IL-33, TSLP) that promote the generation of adaptive CD4+ helper Type 2 cells and humoral products such as allergen-specific IgE. Mast cells and basophils are integral players in this network, serving as primary effectors of IgE-mediated responses. These cells bind IgE via high-affinity IgE receptors (FcεRI) expressed on their surface and, upon activation by allergens, release a variety of mediators that regulate tissue responses, attract and modulate other inflammatory cells, and contribute to tissue repair. Here, we review the biology and effector mechanisms of these cells, focusing primarily on their role in mediating IgE responses in both physiological and pathological contexts.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"331 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741541","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}

{"title":"Correction to “The Journey Toward Disease Modification in Cow Milk Protein Allergy”","authors":"","doi":"10.1111/imr.70022","DOIUrl":"10.1111/imr.70022","url":null,"abstract":"&lt;p&gt;R. Nocerino, L. Carucci, S. Coppola, F. Oglio, A. Masino, A. Agizza, L. Paparo, R. Berni Canani, “The journey toward disease modification in cow milk protein allergy,” &lt;i&gt;Immunological Reviews&lt;/i&gt; 326, no. 1 (2024): 191–202, https://doi.org/10.1111/imr.13372. Epub 2024 Jul 24. PMID: 39046826.&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;Correction of the Acknowledgement Section&lt;/b&gt;\u0000 &lt;/p&gt;&lt;p&gt;With regards to the article in the September 2024 issue of the Journal, the authors wish to correct the Acknowledgement Section due to the lack of the CUP codes related to funding. The correction to the Acknowledgement Section does not affect the results or conclusions of the article. The authors regret the lack.&lt;/p&gt;&lt;p&gt;We apologize for this error.&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;Current Version:&lt;/b&gt;\u0000 &lt;/p&gt;&lt;p&gt;This review was supported by funding from the National Recovery and Resilience Plan, European Union–Next Generation EU (On Foods–Research and Innovation Network on Food and NutritionSustainability, Safety and Security—Working on Foods; codePE0000003), and from the Italian Ministry of Health-HealthOperational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the diet Mediterranean”(Mediterranean Diet for Human Health Lab “MeDiHealthLab”; code T5-AN- 07). The funders had no influence on the review. We thank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publishing facilitated by Università degli Studi di Napoli Federico II, as part of the Wiley-CRUI-CARE agreement.&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;Revised Version:&lt;/b&gt;\u0000 &lt;/p&gt;&lt;p&gt;This review was supported by funding from the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of March 15 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU. Project code PE00000003, Concession Decree No. 1550 of October 11, 2022, adopted by the Italian Ministry of University and Research, CUP E63C22002030007, project title “ON Foods—Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods” and from the Italian Ministry of Health-Health Operational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the Mediterranean diet” (Mediterranean Diet for Human Health Lab, “MeDiHealthLab,” code T5-AN-07, CUP E63C22002570006). The funders had no influence on the review. Wethank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publ","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676606","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}