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。我们最近出版的作品以及另外 初步数据显示MAIT细胞在过敏性呼吸道具有显著的抗炎作用 发炎。我们假设哮喘患者中MAIT细胞的缺陷有助于 加剧了对过敏原的呼吸道炎症反应，并增加了MAIT细胞 数字可能有助于缓解过敏原诱导的呼吸道炎症和高反应性。 使用来自已故器官捐赠者的新鲜肺样本，我们将检查 重症哮喘患者和对照组肺内MAIT细胞的分子特性 无肺部疾病的个人。我们将使用MAIT细胞缺陷小鼠和过继转移 询问MAIT细胞在过敏性呼吸道炎症中的具体作用的策略。最后， 我们将测试一种工程益生菌菌株是否可以增加MAIT细胞的数量 帮助缓解由常见过敏原引起的持续呼吸道炎症。

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.