Key Points
P2Y6 deficiency enhances DC-mediated Th1/Th17 differentiation.
P2Y6 deficiency aggravates the pathogenesis of EAE.
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.
Footnotes
This work was supported by the National Natural Science Foundation of China (81771306, 81072459), the National Key Research and Development Program of China (2016YFC1200400), the Program for New Century Excellent Talents in University (NCET-12-0179), and the Science and Technology Commission of Shanghai Municipality (14140904200).
The online version of this article contains supplemental material.
- Received August 1, 2019.
- Accepted May 14, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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