Molecular nutrition & food research · 2022
GPR109a Regulates Phenotypic and Functional Alterations in Macrophages and the Progression of Type 1 Diabetes.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Zhang Zhaodi, Li Jiahong, Zhang Ming, Li Binbin, Pan XiaoHua, Dong Xiaoliang, Pan Li-Long, Sun Jia
Аннотация
SCOPE: 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.
METHODS AND RESULTS: 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.
CONCLUSION: 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.
METHODS AND RESULTS: 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.
CONCLUSION: 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.