Maintenance of mucosal homeostasis by commensal Th17 cells

共生 Th17 细胞维持粘膜稳态

• 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
• 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

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.

粘膜是常规免疫系统攻击防御入侵病原体的部位。粘膜 也曾被简单地认为是阻止微生物进入无菌环境的惰性屏障 组织中相反，新出现的证据表明，肠道微生物、屏障 上皮细胞，以及对宿主的局部和全身稳态必不可少的免疫系统。 我们最近提供了深入了解如何识别的上皮和先天性成分， 免疫细胞触发特定的免疫反应，为什么这种反应的性质可以促进宿主- 微生物共生而不是完全的微生物排斥。具体来说，我们发现抗原获得 肠道抗原的肠上皮细胞（IEC）驱动非致病性肠道Th 17细胞 反应在这里，我们建议从机制上研究细胞内IEC抗原的命运和作用， 的IEC的过程中，以及所产生的Th 17细胞的表型和功能。我们将解决 本研究通过两个具体的目的来探讨这些机制：1）IEC在外周血T细胞启动中的作用 2）抗炎性骨髓Th 17细胞的产生和功能。我们的研究 解决粘膜免疫对肠道微生物的基本机制，如果成功， 提供IEC功能的新机制，以及产生保护性粘膜T细胞的途径 应答