Metformin Suppresses Gammadelta T17 Cell Differentiation Alleviating DSS-induced Colitis

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2025 Feb 11

PMID 39934569

Authors

Mingzhong Sun

Hongli Liu

Huixiang Ju

Hongmei Chen

Rui Yang

Dongmei Yan

Langping Shen

Aiting Cai

Yaru Zhi

Lihua Xiao

Qinfang Tang

Yungang Wang

Affiliations

Soon will be listed here.

Abstract

Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. Metformin has pleiotropic effects including anti-inflammatory properties and a notable impact on the gut microbiome. γδT17 cells play crucial role in initiating and maintaining intestinal inflammation. The effect of metformin on γδT17 cells remains unclear. This study aims to explore the connection between metformin-mediated ameliorated response in colitis mice and γδT17 cell activity. The role of γδT17 cell inhibition in metformin-mediated colitis amelioration was evaluated in mice. The effect of metformin on γδT17 differentiation and the possible mechanism were evaluated in a set of in vitro experiments. Results showed that the accumulation of γδT17 cells was negatively correlated with metformin treatment in DSS-induced colitis mice. Exogenous γδT17 cells blocked metformin-mediated colitis inhibition. Furthermore, metformin inhibited γδT17 differentiation, which was related to the inhibition of mTOR/RORγt activity. Our results reveal that metformin ameliorates colitis symptoms by suppressing γδT17 differentiation, suggesting a viable strategy against UC, although the mechanism of metformin in inhibiting γδT17 differentiation remains to be further studied.

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