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

• 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
• 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

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。