GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation

Jia-hong Li1,2, Ming Zhang3,4, Zhao-di Zhang3,4, Xiao-hua Pan3,4, Li-long Pan1,2, Jia Sun3,4
1 Department of Pediatric Laboratory, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Jiangnan University, Wuxi 214023, China
2 Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China
3 State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
4 School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
Correspondence to: Li-long Pan:, Jia Sun:,
DOI: 10.1038/s41401-024-01242-7
Received: 7 May 2023
Accepted: 8 February 2024
Advance online: 21 March 2024


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.

Keywords: type 1 diabetes; G protein-coupled receptor 41; short-chain fatty acids; dendritic cells; SOCS3; STAT3

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