Glucocorticoid-Induced Tumor Necrosis Factor Receptor Family-Related Protein Exacerbates Collagen-Induced Arthritis by Enhancing the Expansion of Th17 Cells
Glucocorticoid-Induced Tumor Necrosis Factor Receptor Family-Related Protein Exacerbates Collagen-Induced Arthritis by Enhancing the Expansion of Th17 Cells
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糖皮质激素诱导的肿瘤坏死因子受体家族相关蛋白通过增强 Th17 细胞的扩增加剧胶原诱导的关节炎
DOI：
10.1016/j.ajpath.2011.11.018
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发表时间：
2012-03-01
影响因子：
6
通讯作者：
Lu, Liwei
中科院分区：
文献类型：
--
作者：
Wang, Shengjun;Shi, Ye;Lu, Liwei
kin-17生产。总之，这项研究的结果揭示了GITRL通过增强Th 17细胞的扩增而加剧自身免疫性关节炎的新功能。(Am J Pathol 2012，180：1059-1067; DOI：10.1016/j.ajpath.2011.11.018）风湿性关节炎（RA），一种慢性自身免疫形式的炎性关节疾病，逐渐影响多个关节，在滑膜、软骨和骨中具有病理变化。许多研究表明，A。糖皮质激素诱导的肿瘤坏死因子受体家族相关蛋白（GITR）通过调节先天性和适应性免疫反应在自身免疫性关节炎的发病机制中起关键作用，但GITR激活促进关节炎进展的潜在机制仍不清楚。在这项研究中，我们发现用GEM配体（GITRL）治疗的胶原诱导的关节炎小鼠显示关节炎的早期发作，关节炎症状和关节损伤的严重程度显著增加，其中观察到脾脏和引流淋巴结中的Th 17细胞显著增加。值得注意的是，结果显示，当与GITRL一起培养时，从初始CD 4（+）T细胞诱导了具有增加的ROR γ t mRNA表达的Th 17细胞的显著扩增。一致地，发现用GITRL处理的正常小鼠显示脾Th 17细胞的显著扩增。此外，我们检测到RA患者血清GITRL水平升高，这与白细胞介素-17产生的增加呈正相关。总之，这项研究的结果揭示了GITRL通过增强Th 17细胞的扩增而加剧自身免疫性关节炎的新功能。(Am J Pathol 2012，180：1059-1067; DOI：10.1016/j.ajpath.2011.11.018）
kin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells. (Am J Pathol 2012, 180:1059-1067; DOI: 10.1016/j.ajpath.2011.11.018)Rheumatoid arthritis (RA), a chronic autoimmune form of inflammatory joint disease, progressively affects multiple joints with pathological changes in the synovia, cartilage, and bone. Numerous studies have suggested a. critical role for glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) in the pathogenesis of autoimmune arthritis by modulating both innate and adaptive immune reactions, but the underlying mechanisms by which GITR activation promotes arthritic progression remain largely unclear. In this study, we found that collagen-induced arthritis mice treated with the ligand of GEM (GITRL) displayed an earlier onset of arthritis with a markedly increased severity of arthritic symptoms and joint damage, in which significantly increased Th17 cells in both spleen and draining lymph nodes were observed. Notably, results showed that a marked expansion of Th17 cells with increased ROR gamma t mRNA expression was induced from naive CD4(+) T cells when cultured with GITRL. Consistently, normal mice that were treated with GITRL were found to display a substantial expansion of splenic Th17 cells. Furthermore, we detected elevated serum levels of GITRL in patients with RA, which were positively correlated with an increase in interleu-kin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells. (Am J Pathol 2012, 180:1059-1067; DOI: 10.1016/j.ajpath.2011.11.018)