Key Laboratory of Food Science and Technology, Department of Food Science and Engineering, Jiangnan University, Wuxi, 214122, China.
School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
Mol Nutr Food Res. 2022 Dec;66(23):e2200300. doi: 10.1002/mnfr.202200300. Epub 2022 Oct 20.
Dietary fibers can alter gut microbiota and microbial metabolite profiles. SCFAs are produced by bacterial fermentation of fiber, mediating immune homeostasis through G-protein-coupled receptors (GPCRs). GPR109a, a receptor for niacin and butyrate, expressed by immune cells and non-immune cells, is a key factor regulating immune responses. However, the role and underlying mechanisms of GPR109a in type 1 diabetes (T1D) remain unclear.
Experimental T1D was induced by streptozotocin in GPR109a-deficient (Gpr109a ) and wild type mice. The study found that Gpr109a mice were more susceptible to T1D with dysregulated immune responses, along with increased M1 macrophage polarization (from 10.55% to 21.48%). Further, an adoptive transfer experiment demonstrated that GPR109a-deficient macrophages promoted the homing of intestine-derived type 1 cytotoxic T cells to pancreas (from 18.91% to 24.24%), thus disturbing the pancreatic immune homeostasis in non-obese diabetic mice. Mechanistically, GPR109a deficiency promoted M1 macrophage polarization associated with the activation of suppressor of cytokine signaling 3-signal transducer and activator of transcription 1 signaling pathway.
The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D. Activation of GPR109a on macrophage by dietary components may provide a new strategy for preventing or treating T1D.
膳食纤维可以改变肠道微生物群和微生物代谢物谱。短链脂肪酸（SCFAs）是由细菌对纤维的发酵产生的，通过 G 蛋白偶联受体（GPCR）介导免疫稳态。GPR109a 是烟酸和丁酸盐的受体，由免疫细胞和非免疫细胞表达，是调节免疫反应的关键因素。然而，GPR109a 在 1 型糖尿病（T1D）中的作用和潜在机制尚不清楚。
在 GPR109a 缺陷（Gpr109a ）和野生型小鼠中，用链脲佐菌素诱导实验性 T1D。研究发现，Gpr109a 小鼠对 T1D更敏感，免疫反应失调，M1 巨噬细胞极化增加（从 10.55%增加到 21.48%）。此外，一项过继转移实验表明，GPR109a 缺陷型巨噬细胞促进肠道来源的 1 型细胞毒性 T 细胞向胰腺归巢（从 18.91%增加到 24.24%），从而扰乱非肥胖型糖尿病小鼠的胰腺免疫稳态。机制上，GPR109a 缺乏促进了与抑制细胞因子信号 3-信号转导和转录激活因子 1 信号通路激活相关的 M1 巨噬细胞极化。
研究结果表明，巨噬细胞 GPR109a 缺乏加速了 T1D 的发展。饮食成分激活巨噬细胞上的 GPR109a 可能为预防或治疗 T1D 提供一种新策略。
