Molecular mechanisms underlying ACAID-induction

ACAID 诱导的分子机制

• 批准号: 7735522
• 负责人: SHARMILA MASLI
• 金额: $ 48.94万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7735522
• 关键词: Address; Adoptive Transfer; Angiogenesis Inhibitors; Anti-Inflammatory Agents; Anti-inflammatory; Antigen-Presenting Cells; Autoimmune Diseases; Biological; Chronic; Cornea; Development; Epithelium; Extracellular Matrix Proteins; Eye; Functional disorder; Goals; Graft Rejection; Immune; Immune response; Immunologics; Inflammation; Inflammatory; Inflammatory Response; Investigation; Iris; Knowledge; Lacrimal gland structure; Lead; Maintenance; Mediating; Molecular; Mus; Peptides; Play; Prevention; Process; Property; Regulation; Role; Structure; Testing; Therapeutic; Therapeutic Intervention; Thrombospondin 1; Vision; Work; Wound Healing; angiogenesis; cell type; corneal epithelium; design; improved; insight; novel; ocular surface; prevent; reconstitution; research study

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.

血小板反应蛋白 (TSP-1) 对于维持眼部免疫特权和防止眼部炎症潜在的致盲作用至关重要。细胞外基质蛋白 TSP-1 由多个眼上皮以及常驻抗原呈递细胞 (APC) 合成，有助于眼睛的免疫豁免状态。 TSP-1对眼部的抗炎作用 TSP-1 缺陷小鼠中慢性眼表炎症的自发发展是明显的炎症。本提案中描述的研究旨在阐明在 TSP-1 缺失的情况下引起的炎症反应背后的免疫机制。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重要性。这一目标的实验将使我们能够表征在缺乏 TSP-1 的情况下产生的导致眼表炎症的免疫效应物。第二个目标旨在研究泪腺中局部 TSP-1 对改变免疫效应器的具体贡献。考虑到像 TSP-1 这样的大分子的多结构域结构具有多种细胞类型特异性生物效应，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 对于维持免疫特权很重要，因此这些研究可以进一步建立在眼部免疫反应的现有知识的基础上，并为新的潜在治疗策略提供见解。