Dong LW, Ma ZC, Fu J, Huang BL, Liu FJ, Sun D, Lan C. Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells’ T helper 17 polarization . World J Gastroenterol 2022; 28(25): 2955-2967 [PMID: 35978875 DOI: 10.3748/wjg.v28.i25.2955]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
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 byNational 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 Processing time: 140 Days and 3.3 Hours
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.
