Daniel Lozano-Ojalvo, Xin Chen, Wajiha Kazmi, David Menchén-Martínez, Leticia Pérez-Rodríguez, Weslley Fernandes-Braga, Scott Tyler, Keith Benkov, Nanci Pittman, Joanne Lai, Hugh A Sampson, Maria Curotto de Lafaille, David Dunkin, M Cecilia Berin
{"title":"不同的 Tfh 细胞表型可区分 IgE 介导的牛奶过敏和儿童嗜酸性粒细胞食管炎。","authors":"Daniel Lozano-Ojalvo, Xin Chen, Wajiha Kazmi, David Menchén-Martínez, Leticia Pérez-Rodríguez, Weslley Fernandes-Braga, Scott Tyler, Keith Benkov, Nanci Pittman, Joanne Lai, Hugh A Sampson, Maria Curotto de Lafaille, David Dunkin, M Cecilia Berin","doi":"10.1016/j.jaci.2024.09.024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4<sup>+</sup> T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.</p><p><strong>Objective: </strong>To identify CD4<sup>+</sup> T cell differences between EoE and MA that may be responsible for distinct disease manifestations.</p><p><strong>Methods: </strong>The total and milk-specific CD4<sup>+</sup> T cell phenotype of children with milk allergy (MA), EoE (active or in remission) and controls was measured using spectral flow cytometry of peripheral blood (all groups) or esophageal biopsies (EoE and control).</p><p><strong>Results: </strong>Circulating milk-responsive T cells could be identified in active (A)-EoE and MA. An increased frequency of Th2A cells was also noted in MA and EoE. In circulating T cells, type 2 cytokine production was elevated in MA, but not EoE. Within the milk-responsive Tfh subset, a dichotomy of phenotype was noted: Tfh13 cells predominated in MA, while IL-10-producing Tfh cells predominated in EoE. In the esophagus, CD4<sup>+</sup> T cells were constitutively activated and expressed not only type 2 cytokines, but also IL-10 and IL-21 in A-EoE. There was production of IgG4 from CD38<sup>+</sup> plasma cells in close proximity to CD4<sup>+</sup> T cells. In vitro activation studies demonstrated that IL-10 and IL-21 elicited strong IgG4 responses in B lymphocytes, while IL-4 and IL-13 promoted IgE production.</p><p><strong>Conclusion: </strong>Our studies demonstrate a dichotomy of Tfh responses that may be the basis for the different clinical manifestations to milk in EoE and MA.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Differential Tfh cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.\",\"authors\":\"Daniel Lozano-Ojalvo, Xin Chen, Wajiha Kazmi, David Menchén-Martínez, Leticia Pérez-Rodríguez, Weslley Fernandes-Braga, Scott Tyler, Keith Benkov, Nanci Pittman, Joanne Lai, Hugh A Sampson, Maria Curotto de Lafaille, David Dunkin, M Cecilia Berin\",\"doi\":\"10.1016/j.jaci.2024.09.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4<sup>+</sup> T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.</p><p><strong>Objective: </strong>To identify CD4<sup>+</sup> T cell differences between EoE and MA that may be responsible for distinct disease manifestations.</p><p><strong>Methods: </strong>The total and milk-specific CD4<sup>+</sup> T cell phenotype of children with milk allergy (MA), EoE (active or in remission) and controls was measured using spectral flow cytometry of peripheral blood (all groups) or esophageal biopsies (EoE and control).</p><p><strong>Results: </strong>Circulating milk-responsive T cells could be identified in active (A)-EoE and MA. An increased frequency of Th2A cells was also noted in MA and EoE. In circulating T cells, type 2 cytokine production was elevated in MA, but not EoE. Within the milk-responsive Tfh subset, a dichotomy of phenotype was noted: Tfh13 cells predominated in MA, while IL-10-producing Tfh cells predominated in EoE. In the esophagus, CD4<sup>+</sup> T cells were constitutively activated and expressed not only type 2 cytokines, but also IL-10 and IL-21 in A-EoE. There was production of IgG4 from CD38<sup>+</sup> plasma cells in close proximity to CD4<sup>+</sup> T cells. In vitro activation studies demonstrated that IL-10 and IL-21 elicited strong IgG4 responses in B lymphocytes, while IL-4 and IL-13 promoted IgE production.</p><p><strong>Conclusion: </strong>Our studies demonstrate a dichotomy of Tfh responses that may be the basis for the different clinical manifestations to milk in EoE and MA.</p>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2024-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jaci.2024.09.024\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2024.09.024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:IgE介导的食物过敏和嗜酸性粒细胞食管炎(EoE)是由牛奶引发的常见疾病。这两种疾病中都存在产生 2 型细胞因子的牛奶反应性 CD4+ T 细胞,但牛奶过敏(MA)和嗜酸性粒细胞性食管炎的临床表现却截然不同:目的:确定牛奶过敏和肠易激综合征的 CD4+ T 细胞差异可能是导致不同疾病表现的原因:方法:使用光谱流式细胞术测量外周血(所有组别)或食管活检组织(EoE 和对照组)中牛奶过敏(MA)、EoE(活动期或缓解期)和对照组儿童的总 CD4+ T 细胞表型和牛奶特异性 CD4+ T 细胞表型:结果:在活动性(A)-EoE 和 MA 中可发现循环牛奶反应性 T 细胞。在 MA 和 EoE 中,Th2A 细胞的频率也有所增加。在循环 T 细胞中,2 型细胞因子的产生在 MA 中升高,但在 EoE 中没有升高。在牛奶反应性 Tfh 亚群中,发现了表型的二分法:在 MA 中以 Tfh13 细胞为主,而在 EoE 中则以产生 IL-10 的 Tfh 细胞为主。在食管中,CD4+ T 细胞被持续激活,不仅表达 2 型细胞因子,而且在急性食管炎中还表达 IL-10 和 IL-21。CD38+ 浆细胞在靠近 CD4+ T 细胞处产生 IgG4。体外活化研究表明,IL-10 和 IL-21 在 B 淋巴细胞中引起强烈的 IgG4 反应,而 IL-4 和 IL-13 则促进 IgE 的产生:我们的研究证明了Tfh反应的二分法,这可能是EoE和MA患者对牛奶的不同临床表现的基础。
Differential Tfh cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.
Background: IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4+ T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.
Objective: To identify CD4+ T cell differences between EoE and MA that may be responsible for distinct disease manifestations.
Methods: The total and milk-specific CD4+ T cell phenotype of children with milk allergy (MA), EoE (active or in remission) and controls was measured using spectral flow cytometry of peripheral blood (all groups) or esophageal biopsies (EoE and control).
Results: Circulating milk-responsive T cells could be identified in active (A)-EoE and MA. An increased frequency of Th2A cells was also noted in MA and EoE. In circulating T cells, type 2 cytokine production was elevated in MA, but not EoE. Within the milk-responsive Tfh subset, a dichotomy of phenotype was noted: Tfh13 cells predominated in MA, while IL-10-producing Tfh cells predominated in EoE. In the esophagus, CD4+ T cells were constitutively activated and expressed not only type 2 cytokines, but also IL-10 and IL-21 in A-EoE. There was production of IgG4 from CD38+ plasma cells in close proximity to CD4+ T cells. In vitro activation studies demonstrated that IL-10 and IL-21 elicited strong IgG4 responses in B lymphocytes, while IL-4 and IL-13 promoted IgE production.
Conclusion: Our studies demonstrate a dichotomy of Tfh responses that may be the basis for the different clinical manifestations to milk in EoE and MA.
期刊介绍:
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.