PT  - JOURNAL ARTICLE
AU  - Li, Zhenlong
AU  - He, Cong
AU  - Zhang, Jiang
AU  - Zhang, Hongmei
AU  - Wei, Huan
AU  - Wu, Shijia
AU  - Jiang, Wenzheng
TI  - P2Y<sub>6</sub> Deficiency Enhances Dendritic Cell–Mediated Th1/Th17 Differentiation and Aggravates Experimental Autoimmune Encephalomyelitis
AID  - 10.4049/jimmunol.1900916
DP  - 2020 Jun 17
TA  - The Journal of Immunology
PG  - ji1900916
4099  - http://www.jimmunol.org/content/early/2020/06/14/jimmunol.1900916.short
4100  - http://www.jimmunol.org/content/early/2020/06/14/jimmunol.1900916.full
AB  - P2Y6 deficiency enhances DC-mediated Th1/Th17 differentiation.P2Y6 deficiency aggravates the pathogenesis of EAE.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.