P2Y6 Deficiency Enhances Dendritic Cell-Mediated Th1/Th17 Differentiation and Aggravates Experimental Autoimmune Encephalomyelitis
P2Y6 Deficiency Enhances Dendritic Cell-Mediated Th1/Th17 Differentiation and Aggravates Experimental Autoimmune Encephalomyelitis
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P2Y(6) 缺乏增强树突状细胞介导的 Th1/Th17 分化并加重实验性自身免疫性脑脊髓炎
DOI：
10.4049/jimmunol.1900916
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发表时间：
2020-07-15
影响因子：
4.4
通讯作者：
Jiang, Wenzheng
中科院分区：
文献类型：
--
作者：
Li, Zhenlong;He, Cong;Jiang, Wenzheng
树突状细胞（Dendritic cells，DCs）是一种重要的APC，在启动和调节适应性免疫应答中起着重要作用。在本研究中，我们报道了G蛋白偶联受体成员P2 Y（6）通过抑制转录因子NF-κ B B的活化来抑制DC的成熟和活化。此外，P2 Y（6）的缺失不影响稳态中的T细胞稳态。然而，体外研究表明，P2 Y（6）信号抑制DC介导的IL-12和IL-23的产生以及Th 1和Th 17亚群的极化。此外，我们发现，缺乏P2 Y 6的小鼠发展更严重的实验性自身免疫性脑脊髓炎相比，野生型小鼠。结果提示P2 Y（6）是DC成熟的关键调节因子，P2 Y（6）的缺失导致实验性自身免疫性脑脊髓炎的加重，提示P2 Y（6）可能在自身免疫性疾病的发病机制中起关键作用。
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(6), a member of G protein-coupled receptors, inhibits the maturation and activation of DCs via suppressing the activation of the transcription factor NF-kappa B. Furthermore, loss of P2Y(6) does not impact T cells homeostasis in the steady-state. However, in vitro studies show that P2Y(6) 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 6 develop more severe experimental autoimmune encephalomyelitis compared with wild-type mice. Our results indicate that P2Y(6) functions as a pivotal regulator on DC maturation, and the loss of P2Y(6) results in the aggravated experimental autoimmune encephalomyelitis, which suggests that P2Y(6) may play a pivotal role in the pathogenesis of autoimmune diseases.