Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2022; 28(25): 2955-2967
Published online Jul 7, 2022. doi: 10.3748/wjg.v28.i25.2955
Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells’ T helper 17 polarization
Li-Wei Dong, Zhi-Chao Ma, Jiao Fu, Bai-Li Huang, Fu-Jin Liu, Deming Sun, Cheng Lan
Li-Wei Dong, Zhi-Chao Ma, Jiao Fu, Bai-Li Huang, Fu-Jin Liu, Cheng Lan, Department of Gastroenterology, Hainan General Hospital, Affiliated Hainan Hospital, Hainan Medical University, Haikou 570311, Hainan Province, China
Deming Sun, Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90033, United States
Author contributions: Dong LW and Lan C designed the study and interpreted the findings; Dong LW and Ma ZC performed the experiments, analyzed the data, and drafted the manuscript; Fu J, Huang BL and Liu FJ helped collect and analyze the data; Sun D and Lan C critically revised the manuscript for important intellectual content and reviewed the article; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81160057, No. 81860102, and No. 82060102.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Care and Use Committee of Hainan General Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cheng Lan, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology, Hainan General Hospital, Affiliated Hainan Hospital, Hainan Medical University, No. 19 Xiuhua Road, Xiuying District, Haikou 570311, Hainan Province, China. lancheng71@163.com
Received: February 14, 2022
Peer-review started: February 14, 2022
First decision: April 12, 2022
Revised: April 26, 2022
Accepted: June 13, 2022
Article in press: June 13, 2022
Published online: July 7, 2022
ARTICLE HIGHLIGHTS
Research background

It has been proved that low-grade inflammation and immunological dysfunction are involved in post-infectious irritable bowel syndrome (PI-IBS). T helper 17 (Th17) polarization occurs in IBS. Adenosine and its receptors participate in intestinal inflammation and immune regulation.

Research motivation

To elucidate the pathogenesis of PI-IBS and identify a potential target for the treatment of this disease.

Research objectives

This study aims to explore the role of adenosine 2A receptor (A2AR) in PI-IBS and its underlying mechanism, especially the relationship between A2AR and Th17 response.

Research methods

A PI-IBS model was established by infecting mice with Trichinella spiralis. The expression and function of A2AR and CD4+ T lymphocytes were examined. Furthermore, the effect of A2AR on CD4+ T lymphocyte Th17 polarization was observed and the clinical features of PI-IBS were evaluated.

Research results

The main results can be summarized as follow: (1) expression of ATP and A2AR and inhibition of A2AR improved the clinical features in PI-IBS; (2) CD4+ T cells expressed A2AR and produced IL-17 in vitro, which was regulated by the A2AR agonist and antagonist; and (3) The A2AR antagonist increased the production of IL-17 by CD4+ T cells via the Janus kinase-signal transducer and activator of transcription-receptor-related orphan receptor γ signaling pathway.

Research conclusions

The upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells.

Research perspectives

The present study could provide a new pathway to elucidate the pathogenesis of PI-IBS and identify a novel therapy target for this disease.