Immunological Reviews最新文献

{"title":"Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies","authors":"Quentin Riller,&nbsp;Muriel Schmutz,&nbsp;Jacques Fourgeaud,&nbsp;Alain Fischer,&nbsp;Bénédicte Neven","doi":"10.1111/imr.13402","DOIUrl":"10.1111/imr.13402","url":null,"abstract":"<p>Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"243-264"},"PeriodicalIF":7.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337946","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":"From fat to fire: The lipid–inflammasome connection","authors":"Paras K. Anand","doi":"10.1111/imr.13403","DOIUrl":"10.1111/imr.13403","url":null,"abstract":"<p>Inflammasomes are multiprotein complexes that play a crucial role in regulating immune responses by governing the activation of Caspase-1, the secretion of pro-inflammatory cytokines, and the induction of inflammatory cell death, pyroptosis. The inflammasomes are pivotal in effective host defense against a range of pathogens. Yet, overt activation of inflammasome signaling can be detrimental. The most well-studied NLRP3 inflammasome has the ability to detect a variety of stimuli including pathogen-associated molecular patterns, environmental irritants, and endogenous stimuli released from dying cells. Additionally, NLRP3 acts as a key sensor of cellular homeostasis and can be activated by disturbances in diverse metabolic pathways. Consequently, NLRP3 is considered a key player linking metabolic dysregulation to numerous inflammatory disorders such as gout, diabetes, and atherosclerosis. Recently, compelling studies have highlighted a connection between lipids and the regulation of NLRP3 inflammasome. Lipids are integral to cellular processes that serve not only in maintaining the structural integrity and subcellular compartmentalization, but also in contributing to physiological equilibrium. Certain lipid species are known to define NLRP3 subcellular localization, therefore directly influencing the site of inflammasome assembly and activation. For instance, phosphatidylinositol 4-phosphate plays a crucial role in NLRP3 localization to the <i>trans</i> Golgi network. Moreover, new evidence has demonstrated the roles of lipid biosynthesis and trafficking in activation of the NLRP3 inflammasome. This review summarizes and discusses these emerging and varied roles of lipid metabolism in inflammasome activation. A deeper understanding of lipid-inflammasome interactions may open new avenues for therapeutic interventions to prevent or treat chronic inflammatory and autoimmune conditions.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337943","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":"Immunomodulatory and anti-inflammatory properties of immunoglobulin G antibodies","authors":"Marjan Hematianlarki,&nbsp;Falk Nimmerjahn","doi":"10.1111/imr.13404","DOIUrl":"10.1111/imr.13404","url":null,"abstract":"<p>Antibodies provide an essential layer of protection from infection and reinfection with microbial pathogens. An impaired ability to produce antibodies results in immunodeficiency and necessitates the constant substitution with pooled serum antibodies from healthy donors. Among the five antibody isotypes in humans and mice, immunoglobulin G (IgG) antibodies are the most potent anti-microbial antibody isotype due to their long half-life, their ability to penetrate almost all tissues and due to their ability to trigger a wide variety of effector functions. Of note, individuals suffering from IgG deficiency frequently produce self-reactive antibodies, suggesting that a normal serum IgG level also may contribute to maintaining self-tolerance. Indeed, the substitution of immunodeficient patients with pooled serum IgG fractions from healthy donors, also referred to as intravenous immunoglobulin G (IVIg) therapy, not only protects the patient from infection but also diminishes autoantibody induced pathology, providing more direct evidence that IgG antibodies play an active role in maintaining tolerance during the steady state and during resolution of inflammation. The aim of this review is to discuss different conceptual models that may explain how serum IgG or IVIg can contribute to maintaining a balanced immune response. We will focus on pathways depending on the IgG fragment crystallizable (Fc) as pre-clinical data in various mouse model systems as well as human clinical data have demonstrated that the IgG Fc-domain recapitulates the ability of intact IVIg with respect to its ability to trigger resolution of inflammation. We will further discuss how the findings already have or are in the process of being translated to novel therapeutic approaches to substitute IVIg in treating autoimmune inflammation.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"372-386"},"PeriodicalIF":7.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337944","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":"Loss of tolerance to dietary proteins: From mouse models to human model diseases","authors":"Anais Levescot,&nbsp;Nadine Cerf-Bensussan","doi":"10.1111/imr.13395","DOIUrl":"10.1111/imr.13395","url":null,"abstract":"<p>The critical importance of the immunoregulatory mechanisms, which prevent adverse responses to dietary proteins is demonstrated by the consequences of their failure in two common but distinct human pathological conditions, food allergy and celiac disease. The mechanisms of tolerance to dietary proteins have been extensively studied in mouse models but the extent to which the results in mice can be extrapolated to humans remains unclear. Here, after summarizing the mechanisms known to control oral tolerance in mouse models, we discuss how the monogenic immune disorders associated with food allergy on the one hand, and celiac disease, on the other hand, represent model diseases to gain insight into the key immunoregulatory pathways that control immune responses to food antigens in humans. The spectrum of monogenic disorders, in which the dysfunction of a single gene, is strongly associated with TH2-mediated food allergy suggests an important overlap between the mechanisms that regulate TH2 and IgE responses to food antigens in humans and mice. In contrast, celiac disease provides a unique example of the link between autoimmunity and loss of tolerance to a food antigen.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"173-190"},"PeriodicalIF":7.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259454","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":"Pathogenic mechanisms in the evolution of food allergy","authors":"Monica Martinez-Blanco,&nbsp;Zhussipbek Mukhatayev,&nbsp;Talal A. Chatila","doi":"10.1111/imr.13398","DOIUrl":"10.1111/imr.13398","url":null,"abstract":"<div>\u0000 \u0000 <p>The early development of the neonatal immune system is profoundly influenced by exposure to dietary and microbial antigens, which shapes mucosal tolerance. Successful oral tolerance induction is crucially dependent on microbially imprinted immune cells, most notably the RORγt⁺ regulatory T (Treg) and antigen presenting cells and is essential for preventing food allergy (FA). The development of FA can be envisioned to result from disruptions at key checkpoints (CKPTs) that govern oral tolerance induction. These include gut epithelial sensory and effector circuits that when dysregulated promote pro-allergic gut dysbiosis. They also include microbially imprinted immune regulatory circuits that are disrupted by dysbiosis and pro-allergic immune responses unleashed by the dysregulation of the aforementioned cascades. Understanding these checkpoints is essential for developing therapeutic strategies to restore immune homeostasis in FA.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"219-226"},"PeriodicalIF":7.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259460","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":"Immune responses to food","authors":"Cathryn R. Nagler","doi":"10.1111/imr.13397","DOIUrl":"10.1111/imr.13397","url":null,"abstract":"&lt;p&gt;The enormous variety of antigens present in food is not ignored by the immune system. Dietary antigens are recognized as foreign, and tolerance must be induced. The regulation of both mucosal and systemic non-responsiveness to dietary antigens is therefore a basic physiological process which has drawn experimental interest for many years. Indeed, the first report on the induction of non-responsiveness by a fed antigen was published over one hundred years ago.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Since that time it has become clear that, in keeping with the need to maintain tolerance to dietary antigens, the oral route of antigen administration is uniquely suited to inducing antigen specific non-responsiveness. Experiments in the late 1980s highlighted the practical benefits of oral antigen administration by demonstrating that intragastric delivery of autoantigens, prior to peripheral immunization, protected against the development of autoimmunity in mice.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; This finding was subsequently confirmed in a large variety of animal models of autoimmune, allergic, and inflammatory disease, as well as in models of transplant rejection.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; The generalizability of the observation that oral administration of antigen can protect against the development of antigen-induced systemic disease became the foundation for immunotherapeutic trials of orally administered antigens for several human diseases including rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, autoimmune uveitis and food allergy.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; However, unlike the murine models where the autoantigens were well defined and administered before disease was induced, the clinical trials attempted to modulate established tissue damage in settings in which the autoantigens were both complex and poorly characterized. It was not surprising, then, when these initial trials met with limited success. Both the murine and human studies succeeded, however, in stimulating interest in understanding the mechanisms by which orally administered antigens induce systemic nonresponsiveness to subsequent antigen challenge.&lt;/p&gt;&lt;p&gt;Early work by Weiner and colleagues described high and low dose oral tolerance mediated by deletion or anergy/suppression and a novel subset of TGF-β secreting “Th3” cells.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; The doses designated as high and low were somewhat arbitrarily defined. The identification of transcription factors that specify CD4 T cell differentiation did not reveal a Th3 subset, but did show that the production of TGF-β by innate immune cells is an important fate specifying cytokine for both Th17 cells and peripherally induced Foxp3&lt;sup&gt;+&lt;/sup&gt; regulatory T cells (Tregs).&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; With the discovery of Foxp3&lt;sup&gt;+&lt;/sup&gt; Tregs, attention switched to the role of food antigen specific Tregs induced in the context of the dietary vitamin A metabolite retinoic acid in gut draining lymph nodes. It was even suggested that oral t","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"5-7"},"PeriodicalIF":7.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259456","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 versus IgG and IgA: Differential roles of allergen-specific antibodies in sensitization, tolerization, and treatment of allergies","authors":"E. F. Knol,&nbsp;R. J. J. van Neerven","doi":"10.1111/imr.13386","DOIUrl":"10.1111/imr.13386","url":null,"abstract":"<p>The prevalence of asthma, rhinitis, and food allergies has increased dramatically over the last few decades. This increase originally started in western countries, but is now also evident in many other regions of the world. Given the fact that the increase is so quick, the noted increase cannot be linked to a genetic effect, and many environmental factors have been identified that are associated with increased or reduced prevalence of allergies, like changing dietary habits, increased urbanization, pollution, exposure to microorganisms and LPS, and the farming environment and raw milk consumption. Although the key role of allergen-specific IgE in allergies is well known, the role of allergen-specific IgG and IgA antibodies is less well defined. This review will provide an overview of the functions of allergen-specific IgE in allergy, the role of allergen-specific antibodies (IgG (4) and IgA) in allergen immunotherapy (AIT), the possibility to use allergen-specific antibodies for treatment of ongoing allergies, and the potential role of allergen-specific antibodies in tolerance induction to allergens in a preventive setting. In the last, more speculative, section we will present novel hypotheses on the potential role of allergen-specific non-IgE antibodies in allergies by directing antigen presentation, Th2 development, and innate immune training.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"314-333"},"PeriodicalIF":7.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259458","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":"Regulation of immune responses to food by commensal microbes","authors":"Samuel H. Light,&nbsp;Cathryn R. Nagler","doi":"10.1111/imr.13396","DOIUrl":"10.1111/imr.13396","url":null,"abstract":"<p>The increasing prevalence of immune-mediated non-communicable chronic diseases, such as food allergies, has prompted a deeper investigation into the role of the gut microbiome in modulating immune responses. Here, we explore the complex interactions between commensal microbes and the host immune system, highlighting the critical role of gut bacteria in maintaining immune homeostasis. We examine how modern lifestyle practices and environmental factors have disrupted co-evolved host–microbe interactions and discuss how changes in microbiome composition impact epithelial barrier function, responses to food allergens, and susceptibility to allergic diseases. Finally, we examine the potential of bioengineered microbiome-based therapies, and live biotherapeutic products, for reestablishing immune homeostasis to prevent or treat food allergies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"203-218"},"PeriodicalIF":7.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259459","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":"Enhancing Fc-mediated effector functions of monoclonal antibodies: The example of HexaBodies","authors":"Hilma J. van der Horst,&nbsp;Tuna Mutis","doi":"10.1111/imr.13394","DOIUrl":"10.1111/imr.13394","url":null,"abstract":"<p>Since the approval of the CD20-targeting monoclonal antibody (mAb) rituximab for the treatment of lymphoma in 1997, mAb therapy has significantly transformed cancer treatment. With over 90 FDA-approved mAbs for the treatment of various hematological and solid cancers, modern cancer treatment relies heavily on these therapies. The overwhelming success of mAbs as cancer therapeutics is attributed to their broad applicability, high safety profile, and precise targeting of cancer-associated surface antigens. Furthermore, mAbs can induce various anti-tumor cytotoxic effector mechanisms including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), all of which are mediated via their fragment crystallizable (Fc) domain. Over the past decades, these effector mechanisms have been substantially improved through Fc domain engineering. In this review, we will outline the different approaches to enhance Fc effector functions via Fc engineering of mAbs, with a specific emphasis on the so-called “HexaBody” technology, which is designed to enhance the hexamerization of mAbs on the target cell surface, thereby inducing greater complement activation, CDC, and receptor clustering. The review will summarize the development, preclinical, and clinical testing of several HexaBodies designed for the treatment of B-cell malignancies, as well as the potential use of the HexaBody technology beyond Fc-mediated effector functions.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"328 1","pages":"456-465"},"PeriodicalIF":7.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259463","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":"Maternal influences on offspring food allergy","authors":"Hwa Yeong Lee,&nbsp;Tanuza Nazmul,&nbsp;Jinggang Lan,&nbsp;Michiko K. Oyoshi","doi":"10.1111/imr.13392","DOIUrl":"10.1111/imr.13392","url":null,"abstract":"<div>\u0000 \u0000 <p>The prevalence of allergies has been globally escalating. While allergies could appear at any age, they often develop in early life. However, the significant knowledge gap in the field is the mechanisms by which allergies affect certain people but not others. Investigating early factors and events in neonatal life that have a lasting impact on determining the susceptibilities of children to develop allergies is a significant area of the investigation as it promotes the understanding of neonatal immune system that mediates tolerance versus allergies. This review focuses on the research over the recent 10 years regarding the potential maternal factors that influence offspring allergies with a view to food allergy, a potentially life-threatening cause of anaphylaxis. The role of breast milk, maternal diet, maternal antibodies, and microbiota that have been suggested as key maternal factors regulating offspring allergies are discussed here. We also suggest future research area to expand our knowledge of maternal–offspring interactions on the pathogenesis of food allergy.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"130-150"},"PeriodicalIF":7.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259462","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}