The LSEC-immune interface in liver development and cancer metastasis
There is increasing evidence that immune cell interactions with vascular niches in different organs control both "immune homeostasis" and immune responses. However, the immune-vascular interface remains incompletely understood at both the molecular and cellular level, as well as its role in overall organ (immune) development and function is understudied. Liver sinusoidal endothelial cells (LSECs) form a sinusoidal vascular network in the liver that displays a large surface for the interaction with passenger leukocytes and liver-resident immune cell populations. The most abundant liver lymphocytes comprise tissue-resident innate lymphoid cells (ILCs) and circulatory natural killer (NK) cells that both rapidly react to perturbations of tissue homeostasis. They produce inflammatory cytokines and play critical roles in immune responses against viral and bacterial infection, and malignant disease. In our project, we investigate the innate lymphocyte-LSEC core as the principal unit that regulates liver development, immune tolerance and local immune responses in the context of inflammation and metastatic disease. Our study aims at obtaining a basic understanding of the immune-endothelial crosstalk and the regulation of homeostatic vs defence liver functions by the immune-endothelial axis. The results obtained in our study will identify key mechanisms with the potential to serve as therapeutic targets for the treatment of liver disease.