CNRS Research associate Emma Lefrançais receives grant from the ANR Young Researchers program 2020
Inside Lungs - Lung thrombopoïesis: regulation and function in lung inflammation
Platelets and megakaryocytes are more than clotting agents with key roles in inflammation. Thanks to interaction with leukocytes, endothelial cells and the release of key soluble mediators, platelets are required for lung development, defense and drive hyper inflammation in lung diseases like Acute Respiratory Distress Syndrome (ARDS), cystic fibrosis and asthma.
Megakaryopoiesis and thrombopoiesis are dynamic and adaptive to biological needs and stress conditions like inflammation or infections. Thrombopoiesis outside of the bone marrow has recently been observed in the lung but the specificities, regulation and significance of this local production is unknown. Recent studies and our preliminary data suggest that lung megakaryocytes may have a specific role in inflammation and that platelet biology are altered by lung inflammatory mediators, including by IL-33, a tissue derived alarmin with critical role in airway inflammation and asthma.
The INSIDE LUNGS project proposes to understand lung thrombopoieisis regulation and specificities in vivo and in real time using murine models of lung inflammation, proteomic analysis and cutting edge lung intravital microscopy. Thanks to knockout mice, inhibitors and blocking antibodies, we will evaluate the impact of lung platelets modifications on hyper inflammation and remodeling. The project brings a deeper understanding of lung inflammatory diseases where platelets are known to contribute to dysregulated inflammation (ARDS, asthma, COPD, viral infection…) and will support the discovery of new therapeutic targets.