Immunological Reviews最新文献

{"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}

{"title":"Emerging Concepts in Cytokine Regulation of Airway Remodeling in Asthma","authors":"Jana Latayan,&nbsp;Santhoshi V. Akkenapally,&nbsp;Satish K. Madala","doi":"10.1111/imr.70020","DOIUrl":"10.1111/imr.70020","url":null,"abstract":"<p>Asthma, a chronic respiratory condition that has seen a dramatic rise in prevalence over the past few decades, now affects more than 300 million people globally and imposes a significant burden on healthcare systems. The key pathological features of asthma include inflammation, airway hyperresponsiveness, mucus cell metaplasia, smooth muscle hypertrophy, and subepithelial fibrosis. Cytokines released by lung epithelial cells, stromal cells, and immune cells during asthma are critical to pathological tissue remodeling in asthma. Over the past few decades, researchers have made great strides in understanding key cells involved in asthma and the cytokines that they produce. Epithelial cells as well as many adaptive and innate immune cells are activated by environmental signals to produce cytokines, namely, type 2 cytokines (IL-4, IL-5, IL-13), IFN-γ, IL-17, TGF-β, and multiple IL-6 family members. However, the precise mechanisms through which these cytokines contribute to airway remodeling remain elusive. Additionally, multiple cell types can produce the same cytokines, making it challenging to decipher how specific cell types and cytokines uniquely contribute to asthma pathogenesis. This review highlights recent advances and provides a comprehensive overview of the key cells involved in the production of cytokines and how these cytokines modulate airway remodeling in asthma.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668599","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":"Early-Life Host–Microbial Interactions and Asthma Development: A Lifelong Impact?","authors":"Céline Pattaroni,&nbsp;Benjamin J. Marsland,&nbsp;Nicola L. Harris","doi":"10.1111/imr.70019","DOIUrl":"https://doi.org/10.1111/imr.70019","url":null,"abstract":"<p>Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like <i>Faecalibacterium</i> and <i>Bifidobacterium</i> linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut–lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by <i>Streptococcus</i>, <i>Moraxella</i>, and <i>Haemophilus</i> and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638771","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":"Innate Immunity and Asthma Exacerbations: Insights From Human Models","authors":"Jehan Alladina,&nbsp;Benjamin D. Medoff,&nbsp;Josalyn L. Cho","doi":"10.1111/imr.70016","DOIUrl":"https://doi.org/10.1111/imr.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>Asthma is a common chronic respiratory disease characterized by the presence of airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. Repeated asthma exacerbations can lead to progressive airway remodeling and irreversible airflow obstruction. Thus, understanding and preventing asthma exacerbations are of paramount importance. Although multiple endotypes exist, asthma is most often driven by type 2 airway inflammation. New therapies that target specific type 2 mediators have been shown to reduce the frequency of asthma exacerbations but are incompletely effective in a significant number of asthmatics. Furthermore, it remains unknown whether current treatments lead to sustained changes in the airway or if targeting additional pathways may be necessary to achieve asthma remission. Activation of innate immunity is the initial event in the inflammatory sequence that occurs during an asthma exacerbation. However, there continue to be critical gaps in our understanding of the innate immune response to asthma exacerbating factors. In this review, we summarize the current understanding of the role of innate immunity in asthma exacerbations and the methods used to study them. We also identify potential novel therapeutic targets for asthma and future areas for investigation.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629815","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":"Soluble Factors and Mechanisms Regulated by Sialylated IgG Signaling","authors":"Desmond L. Edwards,&nbsp;Min Huang,&nbsp;Taia T. Wang","doi":"10.1111/imr.70021","DOIUrl":"https://doi.org/10.1111/imr.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammation is a complex biological response that can be both induced and actively suppressed by IgG-Fc gamma receptor (FcγR) interactions. This review explores the role of IgG sialylation in reducing or blocking inflammatory responses. We first revisit foundational studies that established the anti-inflammatory properties of sialylated IgG1 Fc. These early investigations revealed that the sialylated fraction is crucial for intravenous immunoglobulin's (IVIg's) ability to reduce inflammation in many autoinflammatory diseases and defined a paracrine signaling mechanism underlying this activity. Next, we discuss a recently identified mechanism whereby sialylated IgG directly induces RE1-Silencing Transcription Factor (REST) which functions as a transcriptional repressor of NF-κB¹. This mechanism suggests a very broad role for sialylated IgG signaling in inflammation control since NF-κB is a central mediator of responses downstream of diverse activating receptors on both adaptive and innate immune cells. Finally, we review a set of soluble factors that are suppressed by sialylated IgG signaling in the murine airway and in purified human macrophages, providing additional insight into mechanisms by which sialylated IgG contributes to broad inflammatory control.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622452","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 Microbiome in Asthma Heterogeneity: The Role of Multi-Omic Investigations","authors":"Yvonne J. Huang","doi":"10.1111/imr.70015","DOIUrl":"https://doi.org/10.1111/imr.70015","url":null,"abstract":"<p>Asthma is one of the most prevalent and extensively studied chronic respiratory conditions, yet the heterogeneity of asthma remains biologically puzzling. Established factors like exogenous exposures and treatment adherence contribute to variability in asthma risk and clinical outcomes. It is also clear that the endogenous factors of genetics and immune system response patterns play key roles in asthma. Despite significant existing knowledge in the above, divergent clinical trajectories and outcomes are still observed, even among individuals with similar risk profiles, biomarkers, and optimal medical management. This suggests uncaptured biological interactions that contribute to asthma's heterogeneity, for which the role of host microbiota has lately attracted much research attention. This review will highlight recent evidence in this area, focusing on bedside-to-bench investigations that have leveraged omic technologies to uncover microbiome links to asthma outcomes and immunobiology. Studies centered on the respiratory system and the use of multi-omics are noted in particular. These represent a new generation of reverse-translational investigations revealing potential functional crosstalk in host microbiomes that may drive phenotypic heterogeneity in chronic diseases like asthma. Multi-omic data offer a wide lens into ecosystem interactions within a host. This informs new hypotheses and experimental work to elucidate mechanistic pathways for unresolved asthma endotypes. Further incorporation of multi-omics into patient-centered investigations can yield new insights that hopefully lead to even more precise, microbiome-informed strategies to reduce asthma burden.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595570","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":"Correction to “The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities”","authors":"","doi":"10.1111/imr.70017","DOIUrl":"https://doi.org/10.1111/imr.70017","url":null,"abstract":"<p>W. L. Kan, C. M. Weekley, T. L. Nero, et al. “The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities,” <i>Immunological Reviews</i> 329 (2025): e13430, https://doi.org/10.1111/imr.13430.</p><p>In the article, there was an error in the funding grant in the Acknowledgment.</p><p>The second sentence reads:</p><p>Hercus and A.F. Lopez (APP1148221) and Leukemia &amp; Lymphoma Society Chronic Myelomonocytic Leukemia Special Initiative to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).</p><p>The sentence should read:</p><p>Hercus and A.F. Lopez (APP1148221) and the Leukemia &amp; Lymphoma Society with support from the Mike &amp; Sofia Segal Foundation to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).</p><p>We apologize for this error.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"330 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595593","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}