Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation

作者：Peruzzotti Jametti Luca^*; Bernstock Joshua D; Vicario Nunzio; Costa Ana S H; Kwok Chee Keong; Leonardi Tommaso; Booty Lee M; Bicci Iacopo; Balzarotti Beatrice; Volpe Giulio; Mallucci Giulia; Manferrari Giulia; Donega Matteo; Iraci Nunzio; Braga Alice; Hallenbeck John M; Murphy Michael P; Edenhofer Frank^*; Frezza Christian^*; Pluchino Stefano^*

来源：Cell Stem Cell, 2018, 22(3): 355-+.

DOI：10.1016/j.stem.2018.01.020

Neural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the CNS. Metabolites, such as succinate, modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here, we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage. Inflammatory MPs release succinate, which activates succinate receptor 1 (SUCNR1)/GPR91 on NSCs, leading them to secrete prostaglandin E2 and scavenge extracellular succinate with consequential anti-inflammatory effects. Thus, our work reveals an unexpected role for the succinate-SUCNR1 axis in somatic and directly induced NSCs, which controls the response of stem cells to inflammatory metabolic signals released by type 1 MPs in the chronically inflamed brain.

• 出版日期2018-3-1