GPR41 Deficiency Aggravates Type 1 Diabetes in Streptozotocin-treated Mice by Promoting Dendritic Cell Maturation

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2024 Mar 22

PMID 38514862

Authors

Jia-Hong Li

Ming Zhang

Zhao-di Zhang

Xiao-Hua Pan

Li-Long Pan

Jia Sun

Affiliations

Soon will be listed here.

Abstract

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41 mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41 mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41 mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

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