Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastroenterol. Aug 7, 2026; 32(29): 119920
Published online Aug 7, 2026. doi: 10.3748/wjg.119920
Published online Aug 7, 2026. doi: 10.3748/wjg.119920
γδ T cells exacerbate intestinal fibrosis in mice with experimental colitis via activation of the CD73-adenosine receptor-cyclic AMP signaling pathway
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 of Hainan Medical University, Haikou 570311, Hainan Province, China
Dong-Chun Liang, De-Ming 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: Liang DC performed most of the experiments; Ma ZC, Fu J, and Huang BL analyzed the data; Dong LW provided technique support; Sun DM and Liu FJ supervised experiment and wrote the manuscript; Lan C supervised and coordinated the project.
Supported by the National Natural Science Foundation of China, No. 81860102 and No. 82060102; and Hainan Provincial Natural Science Foundation High-Level Talent Project, No. 821RC1116 and No. 822RC818.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Care and Use Committee of Hubei Provincial Center for Disease Control and Prevention (No. 202210177).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Cheng Lan, MD, Chief Physician, Professor, Department of Gastroen
Received: February 10, 2026
Revised: March 17, 2026
Accepted: April 20, 2026
Published online: August 7, 2026
Processing time: 156 Days and 23.3 Hours
Revised: March 17, 2026
Accepted: April 20, 2026
Published online: August 7, 2026
Processing time: 156 Days and 23.3 Hours
Core Tip
Core Tip: This study elucidated a critical pathogenic role for γδ T cells in driving intestinal fibrosis. Mechanistically, these cells promote fibrosis most likely by upregulating the CD73-adenosine receptor-cyclic AMP signaling pathway. Depletion of γδ T cells or pharmacological inhibition of CD73 attenuated fibrogenesis, as evidenced by reduced collagen deposition and profibrotic cytokine expression. Conversely, adoptive transfer of γδ T cells exacerbated disease severity. These findings nominate the γδ T cell-CD73-adenosine receptor-cyclic AMP pathway as a novel and promising therapeutic target for intestinal fibrosis.