Modulation of neuroinflammation by novel endothelial GPCRs

G蛋白偶联受体(GPCRs)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，我们研究了三个迄今尚未在EC生物学中涉及的GPCRs的作用，两个孤立的GPCRs，GPRC5B和GPR153，以及一种在EC中未知表达的代谢物GPCRs，短链脂肪酸受体HCA2。这三种GPCRs均在血脑屏障的EC中上调，以应对炎症反应，初步数据表明，它们的遗传失活改变了EC对白细胞和体液因子的屏障功能。借助三苯氧胺诱导的EC特异性基因敲除小鼠，我们将分析这些新的GPCRs在自身免疫和缺血性神经炎症中的体内功能，并剖析其潜在的分子机制。

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.