Molecular mechanisms underlying ACAID-induction

凝血酶敏感蛋白(TSP-1)对于维持眼部免疫赦免和预防潜在的眼部炎症致盲作用是必不可少的。TSP-1是由多个眼上皮细胞和常驻抗原提呈细胞(APC)合成的一种细胞外基质蛋白，与眼睛的免疫豁免状态有关。TSP-1眼部抗炎作用的研究 在TSP-1缺陷小鼠的慢性眼表炎症的自发发展过程中，炎症是明显的。这项建议中描述的研究试图阐明在没有TSP-1的情况下这种炎症反应的潜在免疫学机制。第一个具体目的是确定凝血酶反应蛋白-1(TSP-1)在预防眼部炎症中的意义。这一目标的实验将使我们能够表征在没有TSP-1的情况下开发的免疫效应器，这些免疫效应器会导致眼表炎症。第二个目的是研究泪腺局部TSP-1对改变免疫效应器的特殊作用。考虑到像TSP-1这样具有多细胞类型特异性生物学效应的大分子的多结构域结构，这些研究将阐明TSP-1有助于预防慢性眼部炎症的机制。由于已知TSP-1在维持免疫赦免中起重要作用，这些研究可以进一步建立在眼部免疫反应现有知识的基础上，并为新的潜在治疗策略提供见解。

Thrombospondin (TSP-1) is essential for maintaining ocular immune privilege and preventing potentially blinding effects of ocular inflammation. An extracellular matrix protein TSP-1 is synthesized by several ocular epithelia as well as resident antigen presenting cells (APCs), which contribute to the immune privilege status of the eye. The anti-inflammatory effects of TSP-1 in ocular inflammation are apparent from the spontaneous development of chronic ocular surface inflammation in TSP-1 deficient mice. The studies described in this proposal seek to elucidate immunologic mechanisms underlying such inflammatory responses noted in the absence of TSP-1. The first specific aim seeks to determine the significance of thrombospondin-1 (TSP-1) in the prevention of ocular inflammation. Experiments in this aim will allow us to characterize immune effectors developed in the absence of TSP-1 that lead to ocular surface inflammation. The second aim seeks to investigate the specific contribution of local TSP-1 in the lacrimal glands towards altering immune effectors. Considering the multidomain structure of a large molecule like TSP-1 with multiple cell type specific biological effects, these investigations will clarify mechanisms by which TSP-1 contributes to the prevention of chronic ocular inflammation. Since TSP-1 is known to be important in maintaining immune privilege these studies can build further on the existing knowledge of ocular immune responses and provide insights into novel potential therapeutic strategies.