Analysis of the mechanism of membranous proteolysis and the immunoregulation for Sjogren's syndrome

干燥综合征膜蛋白水解机制及免疫调节分析

基本信息

批准号：
12307040
负责人：
HAYASHI Yoshio
金额：
$ 27.23万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

Primary Sjogren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/La. The purpose of this research is to elucidate the mechanisms on the development of primary Sjogren's syndrome. Although several candidate autoantigens including α-fodrin have been reported in Sjogren's syndrome, the pathogenic roles of the autoantisens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated α-fodrin proteolysis are involved in the progression of tissue destruction in Sjogren's syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death (AICD) of effector T cells may result in the development of autoimmune exocrinopathy in Sjogren's syndrome. Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens

原发性干燥综合征是一种自身免疫性疾病，其特征是淋巴细胞浸润和唾液腺和泪腺破坏，以及全身产生针对核糖核蛋白 (RNP) 颗粒 SS-A/Ro 和 SS-B/La 的自身抗体。阐明原发性干燥综合征发生的机制，尽管已报道了包括α-胞质蛋白在内的几种候选自身抗原。干燥综合征中，自身抗原在 SS 的发生和进展中的致病作用仍不清楚。最近的证据表明，细胞凋亡途径可能发挥着重要作用。细胞凋亡过程中某些自身抗原的裂解可能会揭示可能诱导自身免疫反应的免疫隐性表位。研究回顾了 Fas 介导的细胞毒性和 caspase 介导的 α-fodrin 蛋白水解参与 Fas 配体 (FasL) 的组织破坏的进展，其受体 Fas 对于外周免疫系统的稳态至关重要。效应 T 细胞激活诱导细胞死亡 (AICD) 的缺陷可能导致干燥综合征中自身免疫性外泌体病的发生。雌激素缺乏影响自身免疫病变的机制尚不清楚，抗雌激素作用可能是致病性自身抗原形成的有效因素