P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner.

Autor:	Chang YY; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China., Huan QC; The State Key Laboratory of Functions and Applications of Medicinal Plants and The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guizhou, China.; Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, China., Peng J; Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, China., Bi WC; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China., Zhai LX; School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China., Chen Y; Department of Surgery, The University of Hong Kong, Hong Kong, Hong Kong SAR, China., Lamb JR; Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, United Kingdom., Shen XC; The State Key Laboratory of Functions and Applications of Medicinal Plants and The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guizhou, China., Bian ZX; School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China., Wu HQ; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China., Cheng YX; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China., Xiao HT; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 10; Vol. 13, pp. 820524. Date of Electronic Publication: 2022 Feb 10 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.820524
Abstrakt:	P2Y1 receptor is a G-protein-coupled receptor that plays a critical role in the immune response of inflammatory bowel diseases. However, its regulatory effects on CD4 + T cell response have not been fully elucidated. The study aimed to characterize the role of P2Y1R in Th17 cell differentiation and colonic inflammation. Our results demonstrated that P2Y1R was significantly increased in the splenocytes of colitic mice, which was positively associated with the expression of RORγt and IL-17A. P2Y1R deficiency significantly ameliorated DSS-induced colitis and its Th17 responses. In parallel, P2Y1R deficiency greatly impaired the differentiation of Th17 cell, down-regulated the mRNA expression of IL-17A and RORγt, and protein expression of RORγt in vitro . More importantly, it was found that P2Y1R deficiency markedly increased AMPK phosphorylation of Th17 polarized CD4 + T cells, and antagonist of AMPK significantly reversed the inhibitory effect of P2Y1R deficiency on Th17 cell generation in vivo and in vitro . Overall, these findings demonstrated that P2Y1R deficiency could suppress Th17 cell differentiation in an AMPK-dependent manner to ameliorate colitis, and P2Y1R can act as an important regulator of Th17 cell differentiation to control colonic inflammation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chang, Huan, Peng, Bi, Zhai, Chen, Lamb, Shen, Bian, Wu, Cheng and Xiao.)
Databáze:	MEDLINE
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