P2Y6 Deficiency Enhances Dendritic Cell–Mediated Th1/Th17 Differentiation and Aggravates Experimental Autoimmune Encephalomyelitis
Zhenlong Li, Cong He, Jiang Zhang, Hongmei Zhang, Huan Wei, Shijia Wu, Wenzheng Jiang
Abstract
Abstract 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 P2Y6, 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 P2Y6 does not impact T cells homeostasis in the steady-state. However, in vitro studies show that P2Y6 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 P2Y6 develop more severe experimental autoimmune encephalomyelitis compared with wild-type mice. Our results indicate that P2Y6 functions as a pivotal regulator on DC maturation, and the loss of P2Y6 results in the aggravated experimental autoimmune encephalomyelitis, which suggests that P2Y6 may play a pivotal role in the pathogenesis of autoimmune diseases.