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

Authors :
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
DonegĂ , Matteo
Iraci, Nunzio
Braga, Alice
Hallenbeck, John M.
Murphy, Michael P.
Edenhofer, Frank
Frezza, Christian
Pluchino, Stefano
Source :
Cell Stem Cell; March 2018, Vol. 22 Issue: 3 p355-368.e13
Publication Year :
2018

Abstract

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.

Details

Language :
English
ISSN :
19345909
Volume :
22
Issue :
3
Database :
Supplemental Index
Journal :
Cell Stem Cell
Publication Type :
Periodical
Accession number :
ejs44906847
Full Text :
https://doi.org/10.1016/j.stem.2018.01.020