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

项目总结/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。我们最近发表的工作， 初步数据表明MAIT细胞在过敏性气道中具有显著的抗炎作用， 炎症我们假设哮喘患者MAIT细胞的缺乏有助于 加重了气道对过敏原的炎症反应， 数字可能有助于减轻过敏原诱导的气道炎症和高反应性。 使用来自已故器官捐赠者的新鲜肺样本，我们将检查其丰度和 重症哮喘患者和正常人肺内MAIT细胞的分子特性 没有肺部疾病的人。我们将使用MAIT细胞缺陷小鼠和过继转移 探究MAIT细胞在过敏性气道炎症中的特定作用的策略。最后， 我们将测试通过工程益生菌菌株增加MAIT细胞的数量是否可以 帮助减轻由常见过敏原引起的持续气道炎症。

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. Our recently published work and additionally preliminary data indicate a striking anti-inflammatory role for MAIT cells in allergic airway inflammation. We hypothesize that a deficiency of MAIT cells in asthma patients contributes to exacerbated airway inflammatory responses to allergens, and that increasing MAIT cell numbers may help alleviate allergen-induced airway inflammation and hyperresponsiveness. Using fresh lung samples from deceased organ donors, we will examine the abundance and molecular properties 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 allergic airway inflammation. Finally, we will test whether boosting the number of MAIT cells by an engineered probiotic strain can help alleviate ongoing airway inflammation induced by common allergens.