Gαq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation
Gαq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation
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Gαq 通过调节 Th1 分化来调节类风湿关节炎的发展
DOI：
10.1155/2017/4639081
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发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Shi, Guixiu
中科院分区：
文献类型：
--
作者：
Wang, Dashan;Liu, Yuan;Shi, Guixiu
含有Gαq的G蛋白是G(q/11)类的重要成员，在哺乳动物细胞中普遍表达。研究发现 G α q 在免疫调节和类风湿性关节炎 (RA) 等自身免疫性疾病的发展中发挥着重要作用。然而，G α q 如何参与 RA 的发病机制尚不完全清楚。在本研究中，我们的目的是找出 G α q 是否通过调节 Th1 分化来控制 RA。我们观察到 RA 患者中 G α q 的表达与标志性 Th1 细胞因子（IFN-γ）的表达呈负相关，这表明 G α q 在 Th1 细胞分化中发挥负作用。通过使用 G α q 敲除 (Gnaq-/-) 小鼠，我们证明 G α q 的缺失会导致 Th1 细胞分化增强。 G α q 阴性通过调节 T-bet 的表达和 STAT4 的活性来调节 Th1 细胞的分化。此外，我们检测到自发发生炎症性关节炎的 Gnaq-/- 骨髓 (BM) 嵌合体中 Th1 细胞的比例增加。总之，研究结果表明 G α q 的缺失促进 Th1 细胞的分化并促进 RA 的发病机制。
The G alpha q-containing G protein, an important member of G(q/11) class, is ubiquitously expressed in mammalian cells. G alpha q has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how G alpha q participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether G alpha q controls RA via regulation of Th1 differentiation. We observed that the expression of G alpha q was negatively correlated with the expression of signature Th1 cytokine (IFN-gamma) in RA patients, which suggests a negative role of G alpha q in differentiation of Th1 cells. By using G alpha q knockout (Gnaq-/-) mice, we demonstrated that loss of G alpha q led to enhanced Th1 cell differentiation. G alpha q negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of G alpha q promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.