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P2Y1R 配体通过依赖 AMPK 的方式抑制 Th17 细胞分化并缓解结肠炎症。

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

机构信息

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

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.

出版信息

Front Immunol. 2022 Feb 10;13:820524. doi: 10.3389/fimmu.2022.820524. eCollection 2022.

DOI:10.3389/fimmu.2022.820524
PMID:35222397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8866175/
Abstract

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 . 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 and . 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.

摘要

P2Y1 受体是一种 G 蛋白偶联受体，在炎症性肠病的免疫反应中发挥着关键作用。然而，其对 CD4 T 细胞反应的调节作用尚未完全阐明。本研究旨在探讨 P2Y1R 在 Th17 细胞分化和结肠炎症中的作用。研究结果表明，P2Y1R 在结肠炎小鼠的脾细胞中显著增加，且与 RORγt 和 IL-17A 的表达呈正相关。P2Y1R 缺失显著改善 DSS 诱导的结肠炎及其 Th17 反应。同时，P2Y1R 缺失严重损害 Th17 细胞的分化，下调 IL-17A 和 RORγt 的 mRNA 表达，以及 RORγt 的蛋白表达。更重要的是，研究发现 P2Y1R 缺失显著增加了 Th17 极化 CD4 T 细胞中 AMPK 的磷酸化，而 AMPK 的拮抗剂则显著逆转了 P2Y1R 缺失对 Th17 细胞生成的抑制作用。综上所述，这些发现表明，P2Y1R 缺失可通过 AMPK 依赖性方式抑制 Th17 细胞分化，从而改善结肠炎，P2Y1R 可作为 Th17 细胞分化的重要调节因子，以控制结肠炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/b9299f2defb2/fimmu-13-820524-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/3481aa972665/fimmu-13-820524-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/8873b557568f/fimmu-13-820524-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/ad988271db6f/fimmu-13-820524-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/c0c28887a1a8/fimmu-13-820524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/260bd9a5f016/fimmu-13-820524-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/b9299f2defb2/fimmu-13-820524-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/3481aa972665/fimmu-13-820524-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/8873b557568f/fimmu-13-820524-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/ad988271db6f/fimmu-13-820524-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/c0c28887a1a8/fimmu-13-820524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/260bd9a5f016/fimmu-13-820524-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b404/8866175/b9299f2defb2/fimmu-13-820524-g006.jpg

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