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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1525469
This article is part of the Research Topic Molecular Mechanisms and Therapeutic Strategies in Inflammation View all 7 articles
Inhibition SIRT1 to Regulate FOXP3 or RORγt Can Restore the Balance of Treg/Th17 Axis in Ulcerative Colitis and Enhance the Anti-inflammatory Effect of Moxibustion
Provisionally accepted- Other, Chengdu, China
Patients with ulcerative colitis (UC) typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear. This study first analyzed RNAseq data from public databases of humans and mice, and found that Treg/Th17 axis disruption is an important feature of UC. Differential gene expression and immune infiltration analysis showed that upstream transcription factors, including Forkhead box P3 (FOXP3), were significantly disrupted. Animal experiments confirmed the changes in the transcription factors mentioned above and found a significant decrease in acetylation levels in UC colitis. Further in vitro cytology experiments were conducted to induce or inhibit the expression of deacetylated factor SIRT1. The results indicate that deacetylase SIRT1 is activated in LPS induced inflammation and disturbed the Treg/Th17 immune balance axis. Finally, in vivo studies, the results have shown that administering EX-527 to inhibit SIRT1 leads to an increasing in FOXP3 expression and a decreasing in RORγt expression in UC colon tissue. In addition, the results indicate that traditional Chinese moxibustion can down regulate the expression of SIRT1, directly affecting the balance of Th17/Treg axis, and the combined use of EX-527 further improves the therapeutic effect of moxibustion. This study suggests that driving SIRT1 to regulate the Treg/Th17 axis is a strategy for treating UC.
Keywords: ulcerative colitis, Acetylation, SIRT1, Moxibustion, Treg/Th17, Intestinal barrier 0
Received: 09 Nov 2024; Accepted: 17 Dec 2024.
Copyright: © 2024 Zhu, Wang, Zuo, Liu, Cao, Wang, Yang, Huang, Huang, Tian, Ping and Wu. 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) or licensor 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.
* Correspondence:
Yuanbing Zhu, Other, Chengdu, China
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