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

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被认为在这一过程中发挥了基础作用，但其细胞来源和分子机制尚不清楚。此外，由于缺乏遗传的小鼠模型，影响IL-1a分泌上游肺调节的因素，如肺微生物区系，仍未得到充分研究。本项目旨在从分子细节上揭示炎症肺中参与IL-1a分泌和感知的调节和信号网络，以及它对肺微生物群保护作用的贡献。因此，复杂和新颖的小鼠遗传模型将被用来阐明IL1a的作用并干扰微生物和宿主之间的通讯。综上所述，该项目可以揭示IL-1a在纤维化中的作用，并有可能找到新的治疗靶点来治疗某些炎症驱动的肺部疾病。

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.