Molecular mechanisms underlying ACAID-induction

血小板反应蛋白（TSP-1）对于维持眼部免疫豁免和预防眼部炎症的潜在致盲作用至关重要。细胞外基质蛋白TSP-1由几种眼上皮细胞以及常驻抗原呈递细胞（APC）合成，其有助于眼的免疫赦免状态。TSP-1的眼内抗炎作用 在TSP-1缺陷小鼠中，炎症的自发发展是明显的。本提案中描述的研究旨在阐明在不存在TSP-1的情况下注意到的这种炎症反应的免疫学机制。第一个具体目标是确定血小板反应蛋白-1（TSP-1）在预防眼部炎症中的意义。在这个目标的实验将使我们能够表征免疫效应的TSP-1的情况下，导致眼表面炎症的发展。第二个目的是研究泪腺中局部TSP-1对改变免疫效应物的特异性贡献。考虑到大分子如TSP-1的多结构域结构具有多种细胞类型特异性生物学效应，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在维持免疫豁免中很重要，因此这些研究可以进一步建立在现有的眼部免疫应答知识的基础上，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.