Modulation of neuroinflammation by novel endothelial GPCRs

G蛋白偶联受体（GPCR）介导多种全身和局部介质的细胞内效应，从而调节内皮细胞（EC）功能。在这里，我们研究了三个GPCR的作用，到目前为止还没有牵连在EC生物学，两个孤儿GPCR，GPRC5B和GPR153，和代谢物GPCR，这是不知道在EC中表达，短链脂肪酸受体HCA2。所有这三种GPCR在血脑屏障的EC中响应于炎症而上调，并且初步数据显示它们的遗传失活改变了白细胞和体液因子的EC屏障功能。在他莫昔芬诱导的EC特异性基因敲除小鼠的帮助下，我们将分析这些新型GPCR在自身免疫性和缺血性神经炎症中的体内功能，并剖析潜在的分子机制。

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.