Role of CD97/ADGRE5 in allergic asthma

CD97/ADGRE5 在过敏性哮喘中的作用

• 批准号: 432108769
• 负责人: Professorin Dr. Gabriela Aust
• 金额: --
• 依托单位: Helmholtz-Zentrum für Umweltforschung (UFZ)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/432108769?language=en
• 关键词: Role; CD97; ADGRE5; allergic; asthma

The central aim of our proposal is to elucidate the role of CD97/ADGRE5 in the development and maintenance of asthma, a considerable public health problem with increasing prevalence. Allergic asthma is an inappropriate T helper cell 2 (Th2)-mediated immune response to harmless allergens which is initiated by signals delivered by antigen presenting cells which activate naïve CD4 T-cells via the T-cell receptor and accessory molecules. CD97, an adhesion G protein-coupled receptor (GPCR) strongly present in immune cells, acts with its ligand CD55 as a costimulatory molecule and activator of naïve CD4+ T-cells. It is an important mediator of neutrophilic migration and host immune defense and is linked to rheumatoid arthritis and multiple sclerosis, but there is no information on the involvement of CD97 in asthma so far. Thus, we will characterize the role of CD97 in asthma pathophysiology in various models of allergic asthma using Cd97-deficient (Cd97-/-) and Cd97-/- chimeric mice. Our own initial data have revealed an obvious worsening of acute asthma after loss of CD97. We will further investigate the impact of the application of an established CD97 antibody, which enriches in the lung, on murine asthma development. To elucidate the underlying mechanisms leading to the asthma-modulating effects in Cd97-/- and CD97 antibody-treated mice, we will apply cell culture and in-vivo adoptive cell transfer methods. Finally, we will evaluate the role of the ligand CD55 and its interaction with CD97 in asthma development using Cd55-/- and Cd55-/-/Cd97-/- chimeric mice. The results of our project will not only provide new insights in the function of CD97 in asthma pathophysiology but may also lead to novel strategies for interventions to face allergic immune diseases.

我们提案的中心目的是阐明 CD97/ADGRE5 在哮喘发生和维持中的作用，哮喘是一个严重的公共卫生问题，且患病率不断增加。过敏性哮喘是一种由辅助 T 细胞 2 (Th2) 介导的针对无害过敏原的不适当的免疫反应，该反应由抗原呈递细胞传递的信号启动，抗原呈递细胞通过 T 细胞受体和辅助分子激活幼稚 CD4 T 细胞。 CD97 是一种强烈存在于免疫细胞中的粘附 G 蛋白偶联受体 (GPCR)，与其配体 CD55 一起作为共刺激分子和初始 CD4+ T 细胞的激活剂。它是中性粒细胞迁移和宿主免疫防御的重要介质，与类风湿性关节炎和多发性硬化症有关，但迄今为止没有关于CD97参与哮喘的信息。因此，我们将使用 Cd97 缺陷型 (Cd97-/-) 和 Cd97-/- 嵌合小鼠来表征 CD97 在各种过敏性哮喘模型中的哮喘病理生理学中的作用。我们自己的初步数据显示，CD97 缺失后急性哮喘明显恶化。我们将进一步研究应用已建立的 CD97 抗体（该抗体在肺部富集）对小鼠哮喘发展的影响。为了阐明导致 Cd97-/- 和 CD97 抗体治疗的小鼠哮喘调节作用的潜在机制，我们将应用细胞培养和体内过继细胞转移方法。最后，我们将使用 Cd55-/- 和 Cd55-/-/Cd97-/- 嵌合小鼠评估配体 CD55 及其与 CD97 的相互作用在哮喘发展中的作用。我们的项目结果不仅将为 CD97 在哮喘病理生理学中的功能提供新的见解，而且还可能导致针对过敏性免疫疾病的干预措施的新策略。