Maintenance of mucosal homeostasis by commensal Th17 cells

共生 Th17 细胞维持粘膜稳态

基本信息

批准号：
10621283
负责人：
Ivaylo Ivanov Ivanov
金额：
$ 56.7万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
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：
2021-08-06 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10621283
关键词：
Address Anti-Inflammatory Agents Antigen Presentation Antigens Automobile Driving Bacteria CD4 Positive T Lymphocytes Carrier Proteins Cell physiology Cells Complex Data Development Disease Endocytosis Epithelial Cells Epithelium Exocytosis Fostering Generations Health Homeostasis Human Immune Immune system Immunology In Vitro Inflammation Inflammatory Interleukin-10 Intestines Investigation Maintenance Microbe Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Nature Pathway interactions Peptides Phenotype Play Process Reaction Regulation Role Sampling Side Sterility Symbiosis T cell response T-Lymphocyte Testing Tissues antigen processing commensal microbes cytokine experimental study factor C gut inflammation immunoreaction in vivo insight intestinal epithelium intestinal homeostasis microbial mucosal site mucosal vaccine novel pathogen prevent programs receptor response sensor transcription factor transcytosis

项目摘要

Mucosa are sites of conventional immune system attack for defense against invasive pathogens. Mucosa were also once regarded simply as inert barriers preventing commensal microbes from accessing sterile tissues. Instead, emerging evidence suggests a complex interplay between commensal microbes, barrier epithelial cells, and the immune system that is essential for local and systemic homeostasis of the host. We have recently provided insight into how recognition of commensal components by epithelial and innate immune cells triggers a specific immune reaction and why the nature of this reaction could foster host- microbe symbiosis instead of outright microbial rejection. Specifically, we showed that antigen acquisition be intestinal epithelial cells (IECs) of commensal antigens drives a non-pathogenic commensal Th17 cell response. Here we propose to mechanistically examine the fate of intracellular IEC antigens and the role of IECs in the process, as well as the phenotype and function of the generated Th17 cells. We will address these mechanism by pursuing two specific aims to explore 1) Role of IECs in priming of commensal T cell responses and 2) Generation and function of anti-inflammatory commensal Th17 cells. Our studies address fundamental mechanisms of mucosal immunity to commensal microbes and if successful will provide novel mechanisms of IEC function, as well as pathways for generation of protective mucosal T cell responses.

粘膜是用于防御侵入性病原体的常规免疫系统攻击部位。粘膜也曾经被视为防止共生微生物进入无菌的惰性障碍组织。取而代之的是，新兴的证据表明共生微生物之间存在复杂的相互作用上皮细胞以及对宿主局部和全身稳态必不可少的免疫系统。我们最近提供了有关上皮和先天对共生组成部分的认识的见解免疫细胞会触发特定的免疫反应，以及为什么该反应的性质可以促进宿主 - 微生物共生，而不是彻底的微生物排斥。具体来说，我们表明抗原采集是共生抗原的肠上皮细胞（IEC）驱动非致病性共生TH17细胞回复。在这里，我们提出机械学检查细胞内IEC抗原的命运和作用在此过程中的IEC以及生成的Th17细胞的表型和功能。我们将解决这些机制通过追求两个探索的特定目的1）IEC在共生T细胞启动中的作用反应和2）抗炎共生Th17细胞的产生和功能。我们的研究解决粘膜免疫对共生微生物的基本机制，如果成功，提供IEC功能的新型机制，以及生成保护性粘膜T细胞的途径回答。