Published online Jul 7, 2022. doi: 10.3748/wjg.v28.i25.2955
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
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.
To elucidate the pathogenesis of PI-IBS and identify a potential target for the treatment of this disease.
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.
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.
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.
The upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells.
The present study could provide a new pathway to elucidate the pathogenesis of PI-IBS and identify a novel therapy target for this disease.