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

• 批准号: 10545066
• 负责人: Xin Li
• 金额: $ 9.7万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545066
• 关键词: Adrenal Cortex Hormones; Affect; Airway Disease; Allergic Bronchopulmonary Aspergillosis; Alternaria; American; Antibiotics; Antifungal Agents; Aspergillus fumigatus; Asthma; Award; CD4 Positive T Lymphocytes; Candida; Candida albicans; Career Mobility; Cells; Cellular biology; Childhood Asthma; Chronic; Chronic Obstructive Pulmonary Disease; Cladosporium; Communities; Cystic Fibrosis; Development; Disease; Dissection; Fungal Antigens; Gnotobiotic; Goals; Growth; Health; Human; Immune; Immune System Diseases; Immune response; Immunity; Immunologic Factors; Immunology; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Bowel Diseases; Inhalation; Intestines; Investigation; Knowledge; Lung; Lung diseases; Mediating; Mentors; Mentorship; Modeling; Molecular; Mononuclear; Mucous Membrane; Mus; Neonatal; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Persons; Phagocytes; Process; Pulmonary Inflammation; Pulmonary Pathology; Regulation; Research; Research Personnel; Role; Shapes; T cell response; T-Cell Activation; T-Lymphocyte; Technical Expertise; Training; airway inflammation; allergic airway disease; allergic airway inflammation; antigen-specific T cells; asthmatic; asthmatic patient; career; cross reactivity; dysbiosis; fungal microbiota; fungus; gut microbiome; gut microbiota; gut-lung axis; high risk; immunoregulation; insight; microbial community; microbiome alteration; migration; novel therapeutics; skill acquisition; standard of care; transcriptomics

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.

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，影响着大约 2500 万美国人和 3.34 亿美国人 世界各地的人们。在哺乳动物肠道中，一个多样化的真菌群落（称为菌群）塑造了局部和肠道菌群。 全身性宿主免疫反应。肠道真菌群落的改变与以下因素密切相关： 炎症性疾病，例如哮喘、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特化吞噬细胞可以介导激活 过敏性气道疾病期间真菌引发的 T 细胞的变化。尽管如此，肠-肺的精确机制 免疫串扰尚不清楚。基于这些初步发现，我们假设肠道共生真菌 启动抗真菌免疫，影响肺部免疫并调节气道炎症的进展。 该项目的目标是了解肠道真菌和宿主之间的分子和细胞相互作用 肺部免疫，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 激活和迁移对免疫介导的气道炎症发展的影响。我的长期目标是 研究肠道共生菌群如何调节肠道-系统轴并影响其他肺部 疾病，例如慢性阻塞性肺病（COPD）和囊性纤维化（CF）。在我的 K99 培训期间，我将受到以下团队的监督 具有分枝菌群、粘膜免疫学、T 细胞生物学和肺部专业知识的导师和科学顾问 疾病。他们将在研究和职业转型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肺免疫技术技能和概念知识 和抗真菌 T 细胞。这个 K99/R00 奖项将使我能够获得深入分析所需的技能 以及对肠道系统轴的了解，旨在创造治疗哮喘、慢性阻塞性肺病、囊性纤维化、 和其他与免疫相关的肺部疾病。