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

项目概要/摘要 哮喘仍然是一个严重的公共卫生威胁，治疗需求未得到满足。的 成功疗法的开发依赖于对免疫系统的更深入了解。 涉及的亚型和途径。MAIT细胞是一种先天性T细胞，可以识别微生物， 核黄素代谢物由MR 1呈递，并且可以通过TCR依赖性和 独立的道路。有趣的是，以前的研究表明， MAIT细胞与人类哮喘MAIT细胞在哮喘发生和发展中的确切作用 然而，恶化仍然未知。我们假设，MAIT细胞的缺乏， 哮喘患者对过敏原的气道炎症反应加剧， 增加MAIT细胞数量可能有助于预防哮喘的发展 和恶化。我们将使用已故器官捐献者的新鲜肺样本， 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细胞缺陷小鼠和过继 转移策略，以询问MAIT细胞在过敏原和空气污染物中的特定作用- 诱发气道炎症。最后，我们将测试是否增加MAIT细胞的数量， 工程益生菌菌株可以帮助预防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.