Function and regulation of mucosal associated invariant T cells in the lung

项目摘要/摘要 哮喘仍然是一个严重的公共卫生威胁，治疗需求得不到满足。这个 开发成功的治疗方法依赖于对免疫的更深入的了解 所涉及的子集和路径。MAIT细胞是先天的T细胞，可以识别微生物 核黄素代谢物由MR1提出，可通过TCR依赖和 独立的小路。有趣的是，先前的研究表明， MAIT细胞和人类哮喘。MAIT细胞在哮喘发生和发展中的确切作用 然而，病情恶化仍不得而知。我们假设MAIT细胞的缺陷 哮喘患者可加重对变应原的呼吸道炎症反应 其他刺激，增加MAIT细胞数量可能有助于预防哮喘的发展 和病情恶化。使用来自已故器官捐赠者的新鲜肺样本，我们将检查 重症哮喘患者肺内MAIT细胞的丰度、异质性和功能 并控制没有肺部疾病的个体。我们将使用MAIT细胞缺陷小鼠和领养小鼠 询问MAIT细胞在过敏原和空气污染物中的具体作用的转移策略- 诱导的呼吸道炎症。最后，我们将测试是否通过以下方式增加MAIT细胞的数量 一种经过改造的益生菌菌株可以帮助防止严重哮喘的发展和恶化。

Project Summary/Abstract Asthma remains a serious public health threat with unmet therapeutic needs. The development of successful therapies relies a more in-depth understanding of the immune subsets and pathways involved. MAIT cells are innate-like T cells that recognize microbial riboflavin metabolites presented by MR1 and can function through both TCR dependent and independent pathways. Interestingly, previous studies indicated an inverse association between MAIT cells and human asthma. The precise role of MAIT cells in asthma development and exacerbation, however, remains unknown. We hypothesize that a deficiency of MAIT cells in asthma patients contributes to exacerbated airway inflammatory responses to allergen and other stimulus, and that increasing MAIT cell numbers may help prevent asthma development and exacerbation. Using fresh lung samples from deceased organ donors, we will examine the abundance, heterogeneity and function of lung-resident MAIT cells in severe asthma patients and control individuals without lung diseases. We will use MAIT cell deficient mice and adoptive transfer strategies to interrogate the specific roles of MAIT cells in allergen and air pollutant- induced airway inflammation. Finally, we will test whether boosting the number of MAIT cells by an engineered probiotic strain can help prevent severe asthma development and exacerbation.