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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，其特征是唾液腺和泪腺淋巴细胞浸润和破坏，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。本研究旨在阐明原发性干燥综合征的发病机制。虽然包括α-fodrin在内的几种候选自身抗原在干燥综合征中已有报道，但其在SS的发生和发展中的致病作用仍不清楚。被合适的自身抗原激活的单个T细胞可能会增殖并形成限制性克隆。最近的证据表明，凋亡通路在T细胞对组织特异性自身抗原的耐受中起着核心作用，并可能驱动自身免疫现象。在细胞凋亡过程中，某些自身抗原的裂解可能揭示出可能诱导自身免疫反应的免疫分泌表位。综述的研究表明，Fas介导的细胞毒性和Caspase介导的α-fodrin蛋白分解参与了干燥综合征组织破坏的进展。Fas配体(FasL)及其受体Fas在外周免疫系统的动态平衡中起着至关重要的作用。可以认为，效应T细胞活化诱导细胞死亡(AICD)的缺陷可能导致干燥综合征自身免疫性外分泌病的发生。尽管雌激素缺乏影响自身免疫损害的机制尚不清楚，但抗雌激素作用可能是致病自身抗原形成的一个重要因素。