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

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...

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Autores principales: Chang, Yao-Yao, Huan, Qiu-Chan, Peng, Jiao, Bi, Wen-Chun, Zhai, Li-Xiang, Chen, Yan, Lamb, Jonathan R., Shen, Xiang-Chun, Bian, Zhao-Xiang, Wu, Hai-qiang, Cheng, Yong-Xian, Xiao, Hai-Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866175/
https://www.ncbi.nlm.nih.gov/pubmed/35222397
http://dx.doi.org/10.3389/fimmu.2022.820524
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author Chang, Yao-Yao
Huan, Qiu-Chan
Peng, Jiao
Bi, Wen-Chun
Zhai, Li-Xiang
Chen, Yan
Lamb, Jonathan R.
Shen, Xiang-Chun
Bian, Zhao-Xiang
Wu, Hai-qiang
Cheng, Yong-Xian
Xiao, Hai-Tao
author_facet Chang, Yao-Yao
Huan, Qiu-Chan
Peng, Jiao
Bi, Wen-Chun
Zhai, Li-Xiang
Chen, Yan
Lamb, Jonathan R.
Shen, Xiang-Chun
Bian, Zhao-Xiang
Wu, Hai-qiang
Cheng, Yong-Xian
Xiao, Hai-Tao
author_sort Chang, Yao-Yao
collection PubMed
description 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.
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spelling pubmed-88661752022-02-25 P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner Chang, Yao-Yao Huan, Qiu-Chan Peng, Jiao Bi, Wen-Chun Zhai, Li-Xiang Chen, Yan Lamb, Jonathan R. Shen, Xiang-Chun Bian, Zhao-Xiang Wu, Hai-qiang Cheng, Yong-Xian Xiao, Hai-Tao Front Immunol Immunology 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. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8866175/ /pubmed/35222397 http://dx.doi.org/10.3389/fimmu.2022.820524 Text en Copyright © 2022 Chang, Huan, Peng, Bi, Zhai, Chen, Lamb, Shen, Bian, Wu, Cheng and Xiao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chang, Yao-Yao
Huan, Qiu-Chan
Peng, Jiao
Bi, Wen-Chun
Zhai, Li-Xiang
Chen, Yan
Lamb, Jonathan R.
Shen, Xiang-Chun
Bian, Zhao-Xiang
Wu, Hai-qiang
Cheng, Yong-Xian
Xiao, Hai-Tao
P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title_full P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title_fullStr P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title_full_unstemmed P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title_short P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner
title_sort p2y1r ligation suppresses th17 cell differentiation and alleviates colonic inflammation in an ampk-dependent manner
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866175/
https://www.ncbi.nlm.nih.gov/pubmed/35222397
http://dx.doi.org/10.3389/fimmu.2022.820524
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