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

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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.