Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China
J Immunol. 2020 Jul 15;205(2):387-397. doi: 10.4049/jimmunol.1900916. Epub 2020 Jun 17.
Dendritic cells (DCs) are essential APCs and play a crucial role in initiating and regulating the adaptive immune response. In this study, we have reported that P2Y, a member of G protein-coupled receptors, inhibits the maturation and activation of DCs via suppressing the activation of the transcription factor NF-κB. Furthermore, loss of P2Y does not impact T cells homeostasis in the steady-state. However, in vitro studies show that P2Y signaling inhibits the production of IL-12 and IL-23 and the polarization of Th1 and Th17 subsets mediated by DCs. In addition, we find that mice lacking P2Y develop more severe experimental autoimmune encephalomyelitis compared with wild-type mice. Our results indicate that P2Y functions as a pivotal regulator on DC maturation, and the loss of P2Y results in the aggravated experimental autoimmune encephalomyelitis, which suggests that P2Y may play a pivotal role in the pathogenesis of autoimmune diseases.
树突状细胞（DCs）是重要的抗原呈递细胞，在启动和调节适应性免疫反应中起着关键作用。在这项研究中，我们报道了 P2Y，一种 G 蛋白偶联受体家族的成员，通过抑制转录因子 NF-κB 的激活来抑制 DC 的成熟和激活。此外，P2Y 的缺失不会影响稳态下 T 细胞的稳态。然而，体外研究表明，P2Y 信号抑制由 DC 介导的 IL-12 和 IL-23 的产生以及 Th1 和 Th17 亚群的极化。此外，我们发现缺乏 P2Y 的小鼠比野生型小鼠发展出更严重的实验性自身免疫性脑脊髓炎。我们的结果表明，P2Y 作为 DC 成熟的关键调节因子发挥作用，而 P2Y 的缺失导致实验性自身免疫性脑脊髓炎加重，这表明 P2Y 可能在自身免疫性疾病的发病机制中发挥关键作用。
