Modulation of neuroinflammation by novel endothelial GPCRs

G-protein-coupled receptors (GPCRs) mediate the intracellular effects of a multitude of systemic and local mediators and thereby modulate endothelial cell (EC) function. Here, we study the role of three GPCRs that have so far not been implicated in EC biology, two orphan GPCRs, GPRC5B and GPR153, and a metabolite GPCR that was not known to be expressed in EC, the short chain fatty acid receptor HCA2. All three GPCRs are upregulated in EC of the blood-brain barrier in response to inflammation, and preliminary data show that their genetic inactivation alters EC barrier function for leukocytes and humoral factors. With the help of tamoxifen-inducible, EC-specific knockout mice, we will analyse the in-vivo function of these novel GPCRs in autoimmune and ischemic neuroinflammation, and dissect the underlying molecular mechanisms.