Evidence map›Paper›PMID 29478844›Full record

ArticleCell stem cell2018

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

Luca Peruzzotti-Jametti, Joshua D Bernstock, Nunzio Vicario, Ana S H Costa, Chee Keong Kwok, Tommaso Leonardi, Lee M Booty, Iacopo Bicci, Beatrice Balzarotti, Giulio Volpe and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed, 1 pooled it
15.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

163 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.

  1. Pooled it
  2. Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Trial
  3. Gut microbes · 2026
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103 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 5 countries.

Luca Peruzzotti-JamettiDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: lp429@cam.ac.uk.
Joshua D BernstockDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK; Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH (NINDS/NIH), Bethesda, MD, USA.
Nunzio VicarioDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Ana S H CostaMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Chee Keong KwokInstitute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
Tommaso LeonardiDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Lee M BootyMRC Mitochondrial Biology Unit, Hills Road, University of Cambridge, Cambridge, UK.
Iacopo BicciDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Beatrice BalzarottiDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Giulio VolpeDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Giulia MallucciDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Giulia ManferrariDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Matteo DonegàDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Nunzio IraciDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK; Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via S. Sofia 97, Catania 95125, Italy.
Alice BragaDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
John M HallenbeckStroke Branch, National Institute of Neurological Disorders and Stroke, NIH (NINDS/NIH), Bethesda, MD, USA.
Michael P MurphyMRC Mitochondrial Biology Unit, Hills Road, University of Cambridge, Cambridge, UK.
Frank EdenhoferInstitute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany; Institute of Molecular Biology and CMBI, Genomics, Stem Cell Biology and Regenerative Medicine, Leopold-Franzens-University Innsbruck, Innsbruck, Austria. Electronic address: frank.edenhofer@uibk.ac.at.
Christian FrezzaMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK. Electronic address: cf366@mrc-cu.cam.ac.uk.
Stefano PluchinoDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: spp24@cam.ac.uk.
University of Cambridge · GBMRC Cancer Unit · GBUniversity of Würzburg · DEMRC Mitochondrial Biology Unit · GBNational Institute of Neurological Disorders and Stroke · US

Funding

Austrian Science Fund FWF I 3029Biotechnology and Biological Sciences Research Council MR/K026682/1Medical Research Council MC_U105663142Medical Research Council MC_UU_00015/3Medical Research Council MC_UU_12022/6Medical Research Council MR/K026682/1Wellcome Trust 110158/Z/15/ZWellcome Trust 110159/Z/15/ZWellcome Trust RRZA/057 RG79423
6 · The paper itself

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.

Indexed as

AnimalsCell LineCentral Nervous SystemChronic DiseaseDinoprostoneFemaleHumansInflammationMacrophagesMice, Inbred C57BLNeural Stem CellsOxidative PhosphorylationReceptors, G-Protein-CoupledSuccinic AcidDinoprostoneGPR91 protein, mouseReceptors, G-Protein-CoupledSuccinic AcidSUCNR1 protein, humancell metabolismexperimental autoimmune encephalomyelitisinflammationmacrophagesmicrogliamultiple sclerosisneural stem cellsregenerative medicinestem cellssuccinate

Identifiers

PMID29478844
PMCPMC5842147
OpenAlexW2788731808

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.