江南大学Jia Sun等研究人员合作发现，GPR41缺乏通过促进树突状细胞成熟来加重链脲佐菌素处理小鼠的1型糖尿病。相关论文于2024年3月21日在线发表在《中国药理学报》上。

研究人员表示，肠道免疫稳态紊乱使易感人群易患1型糖尿病（T1D）。G蛋白偶联受体41（GPR41）是一种主要由肠道微生物群产生的短链脂肪酸（SCFA）受体，在维持肠道平衡中发挥着关键作用。

研究人员探讨了GPR41在T1D进展过程中的作用。在非肥胖糖尿病（NOD）小鼠中，研究人员发现胰腺和结肠中GPR41表达的异常减少与T1D的发生有关。与野生型小鼠相比，GPR41缺失型（Gpr41^-/-）小鼠表现出链脲佐菌素（STZ）诱导的T1D明显加重。此外，Gpr41^-/-小鼠还表现出肠道免疫失调增强，肠道刺激的IFN-γ+ T细胞向胰腺的迁移增加。

在Gpr41^-/-小鼠的骨髓树突状细胞中，细胞因子信号转导抑制因子3（SOCS）的表达明显受到抑制，而STAT3的磷酸化则明显增加，从而促进了树突状细胞（DC）的成熟。此外，Gpr41^-/-小鼠骨髓来源树突状细胞（BMDC）的过继性转移加速了辐照NOD小鼠的T1D。研究人员认为，GPR41对维持肠道和胰腺免疫平衡至关重要，并且是T1D中DC成熟的负调控因子。GPR41可能是T1D的潜在治疗靶点。

附：英文原文

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

Author: Li, Jia-hong, Zhang, Ming, Zhang, Zhao-di, Pan, Xiao-hua, Pan, Li-long, Sun, Jia

Issue&Volume: 2024-03-21

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.

DOI: 10.1038/s41401-024-01242-7

Source: https://www.nature.com/articles/s41401-024-01242-7