Immunological Reviews最新文献

{"title":"All roads lead to IgA: Mapping the many pathways of IgA induction in the gut","authors":"Emily R. Siniscalco,&nbsp;Adam Williams,&nbsp;Stephanie C. Eisenbarth","doi":"10.1111/imr.13369","DOIUrl":"10.1111/imr.13369","url":null,"abstract":"<p>The increasing prevalence of food allergy and related pathologies in recent years has underscored the need to understand the factors affecting adverse reactions to food. Food allergy is caused when food-specific IgE triggers the release of histamine from mast cells. However, other food-specific antibody isotypes exist as well, including IgG and IgA. IgA is the main antibody isotype in the gut and mediates noninflammatory reactions to toxins, commensal bacteria, and food antigens. It has also been thought to induce tolerance to food, thus antagonizing the role of food-specific IgE. However, this has remained unclear as food-specific IgA generation is poorly understood. Particularly, the location of IgA induction, the role of T cell help, and the fates of food-specific B cells remain elusive. In this review, we outline what is known about food-specific IgA induction and highlight areas requiring further study. We also explore how knowledge of food-specific IgA induction can be informed by and subsequently contribute to our overall knowledge of gut immunity.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"66-82"},"PeriodicalIF":7.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750657","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":"The journey toward disease modification in cow milk protein allergy","authors":"Rita Nocerino,&nbsp;Laura Carucci,&nbsp;Serena Coppola,&nbsp;Franca Oglio,&nbsp;Antonio Masino,&nbsp;Alessandra Agizza,&nbsp;Lorella Paparo,&nbsp;Roberto Berni Canani","doi":"10.1111/imr.13372","DOIUrl":"10.1111/imr.13372","url":null,"abstract":"<p>Cow milk protein allergy (CMPA) is one of the most common food allergies in the pediatric age worldwide. Prevalence, persistence, and severity of this condition are on the rise, with a negative impact on the health-related quality of life of the patients and families and on the costs related to its management. Another relevant issue is that CMPA in early life may be the first stage of the “allergic march,” leading to the occurrence of other atopic manifestations later in life, especially asthma, atopic eczema, urticaria, and rhinoconjunctivitis. Thus, “disease modification” options that are able to modulate the disease course of pediatric patients affected by CMPA would be very welcomed by affected families and healthcare systems. In this review, we report the most relevant progress on this topic.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"191-202"},"PeriodicalIF":7.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756011","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":"Whence and wherefore IgE?","authors":"Rifat S. Rahman,&nbsp;Duane R. Wesemann","doi":"10.1111/imr.13373","DOIUrl":"10.1111/imr.13373","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite the near ubiquitous presence of Ig-based antibodies in vertebrates, IgE is unique to mammals. How and why it emerged remains mysterious. IgE expression is greatly constrained compared to other IgH isotypes. While other IgH isotypes are relatively abundant, soluble IgE has a truncated half-life, and IgE plasma cells are mostly short-lived. Despite its rarity, IgE is consequential and can trigger life-threatening anaphylaxis. IgE production reflects a dynamic steady state with IgG memory B cells feeding short-lived IgE production. Emerging evidence suggests that IgE may also potentially be produced in longer-lived plasma cells as well, perhaps as an aberrancy stemming from its evolutionary roots from an antibody isotype that likely functioned more like IgG. As a late derivative of an ancient systemic antibody system, the benefits of IgE in mammals likely stems from the antibody system's adaptive recognition and response capability. However, the tendency for massive, systemic, and long-lived production, common to IgH isotypes like IgG, were likely not a good fit for IgE. The evolutionary derivation of IgE from an antibody system that for millions of years was good at antigen de-sensitization to now functioning as a highly specialized antigen-sensitization function required heavy restrictions on antibody production—insufficiency of which may contribute to allergic disease.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"48-65"},"PeriodicalIF":7.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747038","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":"Irritable bowel syndrome: When food is a pain in the gut","authors":"Hind Hussein,&nbsp;Samuel Van Remoortel,&nbsp;Guy E. Boeckxstaens","doi":"10.1111/imr.13374","DOIUrl":"10.1111/imr.13374","url":null,"abstract":"<div>\u0000 \u0000 <p>Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain-sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"102-116"},"PeriodicalIF":7.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732992","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":"Insights into the clinical, immunologic, and genetic underpinnings of food allergy","authors":"Pamela A. Frischmeyer-Guerrerio,&nbsp;Fernanda D. Young,&nbsp;Ozge N. Aktas,&nbsp;Tamara Haque","doi":"10.1111/imr.13371","DOIUrl":"10.1111/imr.13371","url":null,"abstract":"<p>The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020—a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"162-172"},"PeriodicalIF":7.5,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732991","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":"Mechanisms for initiation of food allergy by skin pre-disposed to atopic dermatitis","authors":"Haoran Gao,&nbsp;Allison E. Kosins,&nbsp;Joan M. Cook-Mills","doi":"10.1111/imr.13367","DOIUrl":"10.1111/imr.13367","url":null,"abstract":"<p>Food allergy can be life-threatening and often develops early in life. In infants and children, loss-of-function mutations in skin barrier genes associate with food allergy. In a mouse model with skin barrier mutations (Flakey Tail, FT+/− mice), topical epicutaneous sensitization to a food allergen peanut extract (PNE), an environmental allergen <i>Alternaria alternata</i> (<i>Alt</i>) and a detergent induce food allergy and then an oral PNE-challenge induces anaphylaxis. Exposures to these allergens and detergents can occur for infants and children in a household setting. From the clinical and preclinical studies of neonates and children with skin barrier mutations, early oral exposure to allergenic foods before skin sensitization may induce tolerance to food allergens and thus protect against development of food allergy. In the FT+/− mice, oral food allergen prior to skin sensitization induce tolerance to food allergens. However, when the skin of FT+/− pups are exposed to a ubiquitous environmental allergen at the time of oral consumption of food allergens, this blocks the induction of tolerance to the food allergen and the mice can then be skin sensitized with the food allergen. The development of food allergy in neonatal FT+/− mice is mediated by altered skin responses to allergens with increases in skin expression of interleukin 33, oncostatin M and amphiregulin. The development of neonate food allergy is enhanced when born to an allergic mother, but it is inhibited by maternal supplementation with α-tocopherol. Moreover, preclinical studies suggest that food allergen skin sensitization can occur before manifestation of clinical features of atopic dermatitis. Thus, these parameters may impact design of clinical studies for food allergy, when stratifying individuals by loss of skin barrier function or maternal atopy before offspring development of atopic dermatitis.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"151-161"},"PeriodicalIF":7.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615415","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":"The right educational environment: Oral tolerance in early life","authors":"Talia R. Cheifetz,&nbsp;Kathryn A. Knoop","doi":"10.1111/imr.13366","DOIUrl":"10.1111/imr.13366","url":null,"abstract":"<p>Oral tolerance promotes the suppression of immune responses to innocuous antigen and is primarily mediated by regulatory T cell (Tregs). The development of oral tolerance begins in early life during a “window of tolerance,” which occurs around weaning and is mediated by components in breastmilk. Herein, we review the factors dictating this window and how Tregs are uniquely educated in early life. In early life, the translocation of luminal antigen for Treg induction is primarily dictated by goblet cell-associated antigen passages (GAPs). GAPs in the colon are negatively regulated by maternally-derived epidermal growth factor and the microbiota, restricting GAP formation to the “periweaning” period (postnatal day 11–21 in mice, 4–6 months in humans). The induction of solid food also promotes the diversification of the bacteria such that bacterially-derived metabolites known to promote Tregs—short-chain fatty acids, tryptophan metabolites, and bile acids—peak during the periweaning phase. Further, breastmilk immunoglobulins—IgA and IgG—regulate both microbial diversity and the interaction of microbes with the epithelium, further controlling which antigens are presented to T cells. Overall, these elements work in conjunction to induce a long-lived population of Tregs, around weaning, that are crucial for maintaining homeostasis in adults.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"326 1","pages":"17-34"},"PeriodicalIF":7.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597970","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":"Ketone body metabolism and the NLRP3 inflammasome in Alzheimer's disease.","authors":"Daniel C Shippy, Abigail H Evered, Tyler K Ulland","doi":"10.1111/imr.13365","DOIUrl":"10.1111/imr.13365","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid-β (Aβ) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aβ and tau pathology, with evidence suggesting the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase-1 activation and secretion of IL-1β and IL-18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and β-hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578431","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":"Autoimmunity and the microbiome","authors":"Laura M. Cox,&nbsp;Vijay K. Kuchroo","doi":"10.1111/imr.13363","DOIUrl":"10.1111/imr.13363","url":null,"abstract":"&lt;p&gt;The gut microbiome is a diverse collection of bacteria, fungi, and viruses that have coevolved with the immune system. The microbiome plays a central role in shaping immunologic development as well as regulating other physiologic processes, including metabolic and neurologic functions. Several of the key mechanisms relate to (a) the activation of innate immune system and induction of specific immune cell subsets by pathogen-associated molecular patterns (PAMPS); (b) microbial adherence to the intestinal epithelia surface; (c) the secretion of immunomodulatory metabolites; and (d) biomimicry. While these interactions may be crucial for normal immunologic development, overactivation of these same microbe-immune signaling pathways may lead to the induction of tissue inflammation and autoimmunity.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This special issue will cover the mechanisms by which the gut microbiome influences autoimmune diseases, including type 1 diabetes (T1D),&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; systemic lupus erythematosus (SLE),&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; rheumatoid arthritis (RA),&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; and multiple sclerosis (MS).&lt;span&gt;&lt;sup&gt;8-10&lt;/sup&gt;&lt;/span&gt; Also covered are considerations for host factors such as genetics, aging, and sex, as well as translation for prevention and treatment of autoimmune disease (Figure 1).&lt;/p&gt;&lt;p&gt;&lt;i&gt;Th17 cells&lt;/i&gt; are highly responsive to the gut microbiota,&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; play a central role in autoimmunity, and also play important roles in tissue repair, and protection against infection.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Major questions in the field relate to (a) what factors determine a pathogenic versus homeostatic/protective Th17 cells and (b) what role the gut microbiota play in shaping these responses. This topic is reviewed by Schnell in this special issue.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In groundbreaking work using single cell sequencing, Schnell and colleagues identified a novel stem-like and self-renewing Th17 population denoted by TCF1&lt;sup&gt;+&lt;/sup&gt; transcription factor and SLAMF6&lt;sup&gt;+&lt;/sup&gt; receptor expression.&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; The stem-like SLAMF6&lt;sup&gt;+&lt;/sup&gt; Th17 cells largely reside in the intestinal mucosa, and migrate to the intestinal mucosal following adoptive transfer. Further, they are depleted by oral antibiotics, suggesting that the gut microbiota plays an essential role in maintaining them. In models of autoimmune diseases, stem-like Th17 cells can differentiate into pathogenic CXCR6&lt;sup&gt;+&lt;/sup&gt; Th17 cells that traffic to the extraintestinal sites where they induce tissue inflammation (e.g., the CNS in EAE). Other studies confirm the finding of the presence of stem-like SLAMF6&lt;sup&gt;+&lt;/sup&gt; Th17 cells in the gut and demonstrate that they can also differentiate into IL-10 producing Th17 cells, which have anti-inflammatory functions. This first article in our special issue on the Autoimmunity and the Microbiome sets the stage to understand specific signaling mechanisms at the mucosal interf","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"325 1","pages":"4-8"},"PeriodicalIF":7.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557650","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":"Cracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment","authors":"Christopher Yau,&nbsp;Jayne S. Danska","doi":"10.1111/imr.13362","DOIUrl":"10.1111/imr.13362","url":null,"abstract":"<p>Type 1 diabetes (T1D) results from a complex interplay of genetic predisposition, immunological dysregulation, and environmental triggers, that culminate in the destruction of insulin-secreting pancreatic β cells. This review provides a comprehensive examination of the multiple factors underpinning T1D pathogenesis, to elucidate key mechanisms and potential therapeutic targets. Beginning with an exploration of genetic risk factors, we dissect the roles of human leukocyte antigen (HLA) haplotypes and non-HLA gene variants associated with T1D susceptibility. Mechanistic insights gleaned from the NOD mouse model provide valuable parallels to the human disease, particularly immunological intricacies underlying β cell–directed autoimmunity. Immunological drivers of T1D pathogenesis are examined, highlighting the pivotal contributions of both effector and regulatory T cells and the multiple functions of B cells and autoantibodies in β-cell destruction. Furthermore, the impact of environmental risk factors, notably modulation of host immune development by the intestinal microbiome, is examined. Lastly, the review probes human longitudinal studies, unveiling the dynamic interplay between mucosal immunity, systemic antimicrobial antibody responses, and the trajectories of T1D development. Insights garnered from these interconnected factors pave the way for targeted interventions and the identification of biomarkers to enhance T1D management and prevention strategies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"325 1","pages":"23-45"},"PeriodicalIF":7.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503734","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}