期刊
CELL STEM CELL
卷 22, 期 3, 页码 355-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.01.020
关键词
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资金
- Italian Multiple Sclerosis Association (AISM) [2010/R/31, 2014/PMS/4]
- United States Department of Defense (DoD) Congressionally Directed Medical Research Programs (CDMRP) [MS140019]
- Italian Ministry of Health [GR08-7]
- European Research Council (ERC) under the ERC-StG grant [260511-SEM_SEM]
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub Acellular Approaches for Therapeutic Delivery'' [MR/K026682/1]
- Evelyn Trust [RG 69865]
- Bascule Charitable Trust [RG 75149]
- Wellcome Trust [RRZA/057 RG79423]
- NIH-OxCam training fellowship
- ERA-Net E-rare research programme
- Austrian Science Fund (FWF)
- German Excellence Initiative
- Intramural Research Program (IRP) of NINDS/NIH
- Medical Research Council UK [MC_U105663142]
- Wellcome Trust Investigator award [110159/Z/15/Z]
- Medical Research Council [MC_U105663142, MC_UU_12022/6, MC_UU_00015/3] Funding Source: researchfish
- MRC [MC_UU_12022/6, MC_UU_00015/3, MC_U105663142] Funding Source: UKRI
- Austrian Science Fund (FWF) [I3029] Funding Source: Austrian Science Fund (FWF)
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.
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