Niche-specific BMP-SMAD responses in lymphatic endothelium

Lymphatic vessels drain interstitial fluid and macromolecules from tissues through lymph nodes into the blood circulation to maintain fluid balances. They also function in immune cell trafficking and resolving inflammation. Impaired functions of lymphatic vessels can cause tissue swelling and chronic inflammation. Lymph nodes are immunological hubs that filter lymph to sense tissue damage, and react to protect the body from inflammation. Lymphatic vessels and lymph node sinuses are lined with lymphatic endothelial cells (LECs). LECs show molecular differences (‘heterogeneity’) that result in important functional differences in various lymphatic beds or niches. Recent scRNAseq studies identified seven distinct LEC subsets in mouse lymph nodes. Some express bone morphogenetic protein (BMP) components differentially indicative of a role of BMP signalling in LEC specialization. Moreover, our preliminary data show that BMP-SMAD signalling in LECs is immunosuppressive in mouse skin. I will investigate the unexplored LEC-specific role of the BMP pathway, known to be critical and targetable in blood vessel diseases. I will study amongst others by scRNAseq the consequences of loss-of-function of the BMP pathway in LECs on LEC specialization and inflammation in dermal ear skin and lymph nodes in mice. This PhD project aims to deliver new insight ultimately contributing in the design of improved treatment of patients with lymphatic vessel disorders and associated inflammation.