Overexpression of CXC Chemokine Ligand 14 Exacerbates Collagen-Induced Arthritis
Overexpression of CXC Chemokine Ligand 14 Exacerbates Collagen-Induced Arthritis
复制标题
DOI：
10.4049/jimmunol.0900525
复制
发表时间：
2010-04-15
影响因子：
4.4
通讯作者：
Han, Shuhua
中科院分区：
文献类型：
--
作者：
Chen, Limo;Guo, Linjie;Han, Shuhua
CXCL 14是一种相对较新的趋化因子，其受体尚未鉴定，功能也未明确。最近，我们发现CXCL 14在自身免疫性关节炎（胶原诱导的关节炎）小鼠模型的关节炎关节中上调。为了研究CXCL 14在自身免疫性关节炎的发展和发病机制中的作用，我们已经产生了在磷酸甘油酸激酶启动子控制下过表达CXCL 14的转基因（Tg）小鼠。结果显示，与野生型对照组相比，CXCL 14-Tg小鼠发生了更严重的关节炎。CXCL 14-Tg小鼠的引流淋巴结显著增大，并且含有数量增加的活化T细胞，特别是CD 44（+）CD 62（低）效应记忆细胞。此外，来自CXCL 14-Tg小鼠的T细胞表现出对胶原II的增强的增殖反应，并产生更高水平的IFN-γ，但不产生IL-4或IL-17。CXCL 14-Tg小鼠的IgG 2a自身抗体水平也升高。这些发现表明CXCL 14在自身免疫性关节炎中起重要作用，这可能对理解人类类风湿性关节炎的致病机制以及最终的治疗干预具有意义。免疫学杂志，2010，184：4455-4459。
CXCL14 is a relatively new chemokine with unidentified receptor and undefined function. Recently, we found that CXCL14 is upregulated in arthritic joints in a mouse model of autoimmune arthritis, collagen-induced arthritis. To examine the role of CXCL14 in the development and pathogenesis of autoimmune arthritis, we have generated transgenic (Tg) mice that overexpress CXCL14 under control of phosphoglycerate kinase promoter. The results showed that CXCL14-Tg mice developed more severe arthritis compared with wild-type controls. The draining lymph nodes of CXCL14-Tg mice were significantly enlarged and contained an increased number of activated T cells, particularly the CD44(+)CD62(low) effector memory cells. In addition, T cells from CXCL14-Tg mice exhibited an enhanced proliferative response against collagen II and produced higher levels of IFN-gamma but not IL-4 or IL-17. CXCL14-Tg mice also had elevated levels of IgG2a autoantibodies. These findings indicated that CXCL14 plays an important role in the autoimmune arthritis, which may have an implication in understanding the pathogenic mechanisms of rheumatoid arthritis in humans and, ultimately, therapeutic interference. The Journal of Immunology, 2010, 184: 4455-4459.