Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-γ
Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-γ
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DOI：
10.1016/j.clim.2008.01.003
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发表时间：
2008-04-01
影响因子：
8.6
通讯作者：
Moudgil, Kama D.
中科院分区：
文献类型：
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作者：
Kim, Eugene Y.;Chi, Howard H.;Moudgil, Kama D.
T细胞介导的疾病如类风湿性关节炎（RA）的发病机制通常在Th 1-Th 2范式的背景下解释：促炎细胞因子的启动/传播，以及Th 2细胞因子的下调。然而，在我们基于RA的药物诱导的关节炎（AA）模型的研究中，我们观察到处于AA恢复期的刘易斯（LEW）（RT. 1（l））大鼠在对分枝杆菌的回忆反应中显示出最高水平的IFN-γ。热休克蛋白65（Bhsp 65），而AA抗性的Wistar-Kyoto（WKY）（RT.1（1））大鼠在疾病诱导后更早地分泌高水平的IFN-γ。然而，在任一菌株中均未观察到IL-10或TGF-β的显著分泌。此外，用自身（大鼠）hsp 65（R465）的肽预处理LEW大鼠，其诱导T细胞主要分泌IFN-γ，提供对AA的保护，并降低致关节炎表位再刺激的T细胞的IL-17表达。这些结果为自身免疫性关节炎的发病机制提供了一个新的视角。(C)2008 Etsevier Inc. All rights reserved.
The pathogenesis of T cell-mediated diseases like rheumatoid arthritis (RA) has typically been explained in the context of the Th1-Th2 paradigm: the initiation/propagation by pro-inflammatory cytokines, and downregulation by Th2 cytokines. However, in our study based on the adjuvant-induced arthritis (AA) model of RA, we observed that Lewis (LEW) (RT.1(l)) rats at the recovery phase of AA showed the highest level of IFN-gamma in recall response to mycobacterial. heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1(l)) rats secreted high levels of IFN-gamma much earlier following disease induction. However, no significant secretion of IL-10 or TGF-beta was observed in either strain. Furthermore, pre-treatment of LEW rats with a peptide of self (rat) hsp65 (R465), which induced T cells secreting predominantly IFN-gamma, afforded protection against AA and decreased IL-17 expression by the arthritogenic epitope-restimulated T cells. These results provide a novel perspective on the pathogenesis of autoimmune arthritis. (C) 2008 Etsevier Inc. All rights reserved.