The danger signals in autoimmune uveitis

描述(申请人提供)：T细胞介导的自身免疫性葡萄膜炎是美国和世界范围内致盲的主要原因，特别是在相对年轻和工作的人群中。建议的研究将集中在慢性自身免疫性葡萄膜炎发病机制中的危险信号，使用过继转移光感受器间视黄醇结合蛋白(IRBP)特异性T细胞诱导的小鼠模型。这项提案中描述的目标将检查葡萄膜源性IRBP特异性T细胞启动的危险信号的释放，以及它们在眼部炎症中的作用。目的1研究视网膜细胞与IRBP特异性T细胞相互作用后快速释放HMGB1的Fas/FasL信号转导途径。目的2研究HMGB1在慢性眼内炎症中维持和促进IRBP特异性T细胞功能中的作用。这些研究的结果将进一步加深我们对自身免疫性葡萄膜炎分子发病机制的理解，并确定抗炎干预的新靶点，以限制视力损失。

DESCRIPTION (provided by applicant): Autoimmune uveitis mediated by T cells is a major cause of blindness in the USA and worldwide, particularly among relative young and working populations. Proposed studies will focus on the danger signals in pathogenesis of chronic autoimmune uveitis using a murine model induced by the adoptive transfer of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells. Aims described in this proposal will examine the release of danger signals initiated by uveitogenic IRBP-specific T cells, and the role of them in ocular inflammation. Aim 1 will determine the Fas/FasL signaling in rapid release of HMGB1 from viable retinal cells after interaction with IRBP-specific T cells. Aim 2 will examine the roleof HMGB1 in sustaining and promoting IRBP-specific T cell function during chronic intraocular inflammation. Results of these studies will further our understanding of the molecular pathogenesis of autoimmune uveitis and identify novel targets for anti-inflammatory intervention to limit visual loss.