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

肺粘膜相关不变T细胞的功能和调节

基本信息

批准号：
10646480
负责人：
Qi yang
金额：
$ 55.66万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-11-24 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646480
关键词：
1 year old 7 year old Adoptive Transfer Adult Allergens Alternaria Anabolism Anti-Inflammatory Agents Asthma Biology Biopsy Biopsy Specimen Brain Death Bronchi CD4 Positive T Lymphocytes Cell Count Cells Child Data Development Engineered Probiotics Escherichia coli Exhibits Frequencies Genes House Dust Mite Allergens Human Immune Impairment Individual Inflammatory Inflammatory Response Lung Lung diseases Lymphoid Cell Mediating Metabolic Molecular Mucous Membrane Mus Organ Donor Pathogenicity Pathway interactions Probiotics Production Proliferating Property Public Health Publishing Regulation Repression Riboflavin Risk Role Sampling Sputum Structure of parenchyma of lung T-Lymphocyte Testing Therapeutic Work airway hyperresponsiveness airway immune response airway inflammation allergic airway inflammation asthmatic patient cellular engineering combat insight microbial mouse model novel novel strategies peripheral blood respiratory examination response single-cell RNA sequencing

项目摘要

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.

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。这成功疗法的开发依赖于对免疫的更深入了解涉及的子集和途径。 MAIT 细胞是识别微生物的先天性 T 细胞核黄素代谢物由 MR1 呈现，可以通过 TCR 依赖性和独立的途径。有趣的是，之前的研究表明，两者之间存在负相关关系。 MAIT 细胞和人类哮喘。 MAIT 细胞在哮喘发生和发展中的精确作用然而，恶化情况仍然未知。我们最近发表的作品以及另外初步数据表明 MAIT 细胞在过敏性气道中具有显着的抗炎作用炎。我们假设哮喘患者中 MAIT 细胞的缺乏会导致加剧气道对过敏原的炎症反应，并且增加 MAIT 细胞数字可能有助于减轻过敏原引起的气道炎症和高反应性。使用已故器官捐献者的新鲜肺部样本，我们将检查其丰度和严重哮喘患者和对照肺驻留 MAIT 细胞的分子特性没有肺部疾病的人。我们将使用 MAIT 细胞缺陷小鼠并进行过继转移探讨 MAIT 细胞在过敏性气道炎症中具体作用的策略。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有助于缓解由常见过敏原引起的持续气道炎症。