The impact of microbiome mediated IL-1a signaling in lung fibrosis

微生物介导的 IL-1a 信号传导对肺纤维化的影响

• 批准号: 447836288
• 负责人: Dr. Lara Kern
• 金额: --
• 依托单位: Department of Systems Immunology
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/447836288?language=en
• 关键词: impact; microbiome; mediated; IL; 1a

Chronic lung diseases are accompanied with chronic inflammation and fibrosis and are a common cause of tissue dysfunction, driving common morbidity and mortality. However, immune mechanisms linking fibrosis to chronic inflammation in the lung remain elusive. The cytokine IL-1a is suggested to play a fundamental role in this process, but the cellular source and molecular mechanism remain unknown. Moreover, factors impacting upstream pulmonary regulation of IL-1a secretion, such as the lung microbiota repertoire, remain understudied due to the lack of genetic mouse models. This project aims to unravel in molecular detail the regulation, and signaling network involved in IL-1a secretion and sensing in the inflammation-ridden lungs and its contribution to the protective effects of the lung-microbiome. Thereby, sophisticated and novel genetic mouse models will be used to elucidate the role of IL1a and interfere with the communication between microbiome and the host organism. In summary, this project allows to unravel the role of IL-1a in fibrosis and to potentially allows to find new therapeutic targets to treat certain inflammation-driven lung diseases.

慢性肺部疾病伴有慢性炎症和纤维化，是组织功能障碍的常见原因，导致常见的发病率和死亡率。然而，将纤维化与肺部慢性炎症联系起来的免疫机制仍然难以捉摸。细胞因子IL-1a在此过程中起着重要作用，但其细胞来源和分子机制尚不清楚。此外，由于缺乏遗传小鼠模型，影响IL-1a分泌的上游肺调节的因素，如肺微生物群库，仍然研究不足。该项目旨在从分子细节上揭示炎症缠身的肺部中IL-1a分泌和感知所涉及的调控和信号网络及其对肺部微生物组保护作用的贡献。因此，复杂和新颖的遗传小鼠模型将用于阐明IL 1a的作用并干扰微生物组与宿主生物体之间的通信。总之，该项目允许解开IL-1a在纤维化中的作用，并可能允许找到新的治疗靶点来治疗某些炎症驱动的肺部疾病。