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Humoral Immunoregulation of Allergic Disease by Follicular T Cell Subsets

滤泡 T 细胞亚群对过敏性疾病的体液免疫调节

基本信息

批准号：
10373108
负责人：
Peter The Sage
金额：
$ 50.95万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-16 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10373108
关键词：
Adoptive Transfer Affect Allergens Allergic Disease Allergic inflammation Antibodies Antibody Response B-Lymphocytes Biological Assay Cells Communication Data Development Disease Effector Cell Eosinophilia Equilibrium Evolution Goals Helper-Inducer T-Lymphocyte Hypersensitivity IgE Immune response Immune system Immunoglobulin Class Switching Immunoglobulin Somatic Hypermutation Immunoglobulin Switch Recombination In Vitro Incidence Individual Inflammation Lead Mediating Modeling Mosaicism Mus Pathogenicity Plasma Cells Population Production Publishing Pulmonary Inflammation Pulmonary Pathology Reporter Role Signal Transduction T-Lymphocyte T-Lymphocyte Subsets Testing Time Tissues allergic airway disease base conditional knockout counterregulation dimensional analysis high dimensionality immunoregulation in vitro Assay in vivo innovation mouse model novel novel therapeutics response stem targeted treatment tool

项目摘要

Pathogenic antibodies promote and exacerbate allergic inflammation. Antibody responses are controlled by a delicate balance between stimulatory signals from T follicular helper (Tfh) cells and inhibitory signals from T follicular regulatory (Tfr) cells. Alterations in this balance can lead to pathogenic antibody responses and disease. Although subsets of Tfh and Tfr cells have been implicated in controlling allergies, the precise mechanisms of how these cells regulate distinct stages of allergic inflammation are not currently known. We hypothesize that individual subsets of Tfh and Tfr cells have unique and multifaceted roles during distinct stages of allergic inflammation. Moreover, we hypothesize that the composition of Tfh and Tfr subsets evolves over time to orchestrate allergic disease. By elucidating how Tfh and Tfr cell subsets control allergic inflammation, new strategies can be developed that specifically target pathogenic responses during allergies without affecting broad immune responses. To test these hypotheses, we have developed a number of novel mouse models for the in-depth study of the roles of specialized subsets of Tfh and Tfr cells in allergies. Our aims are to 1) Determine how Tfr cells control allergic inflammation through regulating B, Tfh13 and Tfh21 cells; and 2) Assess how the evolving composition of unique Tfh cell subsets orchestrates allergic inflammation. Our goals are to elucidate mechanisms used by Tfh and Tfr cell subsets to regulate allergies, and to identify targeted strategies to limit allergic inflammation.

致病性抗体促进和加剧过敏性炎症。抗体反应是由一种来自T滤泡辅助细胞（Tfh）的刺激信号和来自T细胞的抑制信号之间的微妙平衡滤泡调节细胞（Tfr）。这种平衡的改变可能导致致病性抗体反应，疾病虽然Tfh和Tfr细胞的亚群与控制过敏有关，但确切的Tfh和Tfr细胞亚群与过敏有关。这些细胞如何调节变应性炎症的不同阶段的机制目前尚不清楚。我们假设Tfh和Tfr细胞的个体亚群在不同阶段具有独特和多方面的作用，过敏性炎症此外，我们假设Tfh和Tfr子集的组成随着时间的推移而演变。是时候安排过敏性疾病了通过阐明Tfh和Tfr细胞亚群如何控制过敏性炎症，可以开发新的策略，专门针对变态反应期间的致病反应，广泛的免疫反应。为了验证这些假设，我们开发了一些新的小鼠模型，深入研究Tfh和Tfr细胞特化亚群在过敏中的作用。我们的目标是1）确定Tfr细胞如何通过调节B、Tfh 13和Tfh 21细胞来控制变应性炎症;以及2）评估独特的Tfh细胞亚群的进化组成如何协调过敏性炎症。我们的目标是阐明Tfh和Tfr细胞亚群调节过敏的机制，并确定靶向策略来抑制过敏性炎症