Mechanistic Investigation of Gut Mycobiota in the Regulation of Lung Immunity and Disease

肠道菌群调节肺部免疫和疾病的机制研究（PA-20-188） 项目概要/摘要 哮喘是一种常见的慢性气道炎症，影响约2500万美国人和3.34亿人。 世界各地的人们。在哺乳动物的肠道中，一种多样的真菌群落，称为真菌生物群， 系统性宿主免疫反应。肠道真菌群落的改变与 炎症性疾病，如哮喘、慢性阻塞性肺病（COPD）和炎症性肠病 疾病（IBD）。我们最近的研究结果表明，肠道专门的吞噬细胞可以介导激活 在过敏性气道疾病中的真菌致敏T细胞。尽管如此，肠肺的确切机制 免疫串扰是未知。基于这些初步发现，我们假设肠道真菌 启动抗真菌免疫，影响肺免疫并调节气道炎症的进展。 本项目的目的是了解肠道真菌和宿主之间的分子和细胞相互作用 肺免疫，特别关注T细胞。虽然目前的建议是阐明肠道的基本作用， 真菌对肺部免疫和疾病的影响，并揭示肠道引发的抗真菌T细胞的机制见解 活化和迁移对免疫介导的气道炎症的发展。我的长期目标是 研究肠道菌群如何调节肠道-全身轴并影响其他肺部 疾病，如COPD和囊性纤维化（CF）。在我的K99培训期间，我将由一个 导师和科学顾问，在真菌生物群，粘膜免疫学，T细胞生物学和肺 疾病他们将在研究和职业过渡方面提供强有力的支持和指导， 独立性，并帮助我发展必要的技术技能和肺免疫的概念知识 和抗真菌T细胞。这个K99/R 00奖项将使我获得深入分析所需的技能 以及对肠道-系统轴的理解，目的是创造治疗哮喘、COPD、CF的新疗法， 和其他免疫相关的肺部疾病。

Mechanistic Investigation of Gut Mycobiota in the Regulation of Lung Immunity and Disease (PA-20-188) Project summary/Abstract Asthma is a common, chronic airway inflammation that affects around 25 million Americans and 334 million people worldwide. In the mammalian gut, a diverse fungal community, known as the mycobiota shapes local and systemic host immune responses. Alterations of the gut fungal community are strongly associated with inflammatory disorders such as asthma, chronic obstructive pulmonary disease (COPD), and inflammatory bowel diseases (IBD). Our recent findings suggest that intestinal specialized phagocytes could mediate the activation of fungal-primed T cells during allergic airway disease. Despite these, the precise mechanisms of gut- lung immune crosstalk are unknown. Based on these preliminary findings, we hypothesize that gut commensal fungi initiate antifungal immunity that affects lung immunity and modulates the progression of airway inflammation. The objectives of this project are to understand the molecular and cellular interplay between gut fungi and host lung immunity with specific focus on T cells. While the current proposal is to illuminate the basic effects of gut fungi on lung immunity and disease and to uncover mechanistic insights about gut-primed antifungal T cell activation and migration on the development of immune-mediated airway inflammation. My long-term goal is to investigate how the gut commensal mycobiota modulates the gut-systemic axis and impacts other pulmonary diseases, such as COPD and cystic fibrosis (CF). During my K99 training, I will be supervised by a team of mentors and scientific advisors with expertise in mycobiota, mucosal immunology, T cell biology and pulmonary diseases. They will provide strong support and mentorship in both research and career transition to independence, and help me to develop necessary technical skills and conceptual knowledge on lung immunity and antifungal T cells. This K99/R00 award will enable me to acquire the skills necessary for a deep analysis and understanding of the gut-systemic axis with the goal of creating novel therapies to treat asthma, COPD, CF, and other immune-related pulmonary diseases.