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Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation.
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; Donegà, Matteo; Iraci, Nunzio; Braga, Alice; Hallenbeck, John M; Murphy, Michael P; Edenhofer, Frank; Frezza, Christian; Pluchino, Stefano.
Afiliación
  • Peruzzotti-Jametti L; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: lp429@cam.ac.uk.
  • Bernstock JD; Department 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.
  • Vicario N; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Costa ASH; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
  • Kwok CK; Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
  • Leonardi T; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Booty LM; MRC Mitochondrial Biology Unit, Hills Road, University of Cambridge, Cambridge, UK.
  • Bicci I; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Balzarotti B; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Volpe G; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Mallucci G; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Manferrari G; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Donegà M; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Iraci N; Department 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.
  • Braga A; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Hallenbeck JM; Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH (NINDS/NIH), Bethesda, MD, USA.
  • Murphy MP; MRC Mitochondrial Biology Unit, Hills Road, University of Cambridge, Cambridge, UK.
  • Edenhofer F; Institute 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.
  • Frezza C; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK. Electronic address: cf366@mrc-cu.cam.ac.uk.
  • Pluchino S; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: spp24@cam.ac.uk.
Cell Stem Cell ; 22(3): 355-368.e13, 2018 03 01.
Article en En | MEDLINE | ID: mdl-29478844
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sistema Nervioso Central / Ácido Succínico / Células-Madre Neurales / Inflamación / Macrófagos Límite: Animals / Female / Humans Idioma: En Revista: Cell Stem Cell Año: 2018 Tipo del documento: Article
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sistema Nervioso Central / Ácido Succínico / Células-Madre Neurales / Inflamación / Macrófagos Límite: Animals / Female / Humans Idioma: En Revista: Cell Stem Cell Año: 2018 Tipo del documento: Article