TRAIL基因敲除小鼠中胸腺细胞凋亡缺陷与自身免疫性疾病加速

Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/- mice.

作者信息

Lamhamedi-Cherradi Salah-Eddine, Zheng Shi-Jun, Maguschak Kimberly A, Peschon Jacques, Chen Youhai H

机构信息

Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Nat Immunol. 2003 Mar;4(3):255-60. doi: 10.1038/ni894. Epub 2003 Feb 10.

DOI:10.1038/ni894

PMID:12577054

Abstract

TRAIL, the tumor necrosis factor-related apoptosis-inducing ligand, selectively induces apoptosis of tumor cells, but not most normal cells. Its role in normal, nontransformed tissues is not clear. We report here that mice deficient in TRAIL have a severe defect in thymocyte apoptosis-thus, thymic deletion induced by T cell receptor ligation is severely impaired. TRAIL-deficient mice are also hypersensitive to collagen-induced arthritis and streptozotocin-induced diabetes and develop heightened autoimmune responses. Thus, TRAIL mediates thymocyte apoptosis and is important in the induction of autoimmune diseases.

摘要

肿瘤坏死因子相关凋亡诱导配体（TRAIL）可选择性地诱导肿瘤细胞凋亡，但对大多数正常细胞无此作用。其在正常未转化组织中的作用尚不清楚。我们在此报告，缺乏TRAIL的小鼠在胸腺细胞凋亡方面存在严重缺陷，因此，由T细胞受体连接诱导的胸腺细胞缺失严重受损。缺乏TRAIL的小鼠对胶原诱导的关节炎和链脲佐菌素诱导的糖尿病也高度敏感，并产生增强的自身免疫反应。因此，TRAIL介导胸腺细胞凋亡，在自身免疫性疾病的诱导中起重要作用。