Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation.

Nature Medicine
Francesca FallarinoR Di Marco

Abstract

High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper (T(H)17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling-which would normally decrease intracellular cAMP formation-biased T(H) cell commitment to the T(H)17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T (T(reg)) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis.

References

Jan 1, 1997·Annual Review of Pharmacology and Toxicology·P J Conn, J P Pin
Feb 18, 1998·European Journal of Clinical Investigation·J F StoverO S Kempski
Apr 1, 1998·Nature·J Banchereau, R M Steinman
Dec 29, 1999·Nature Medicine·D PittC S Raine
Oct 9, 2002·Nature Immunology·Ursula GrohmannPaolo Puccetti
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ursula GrohmannPaolo Puccetti
May 28, 2004·Nature Immunology·Lawrence Steinman
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Mar 11, 2005·Brain : a Journal of Neurology·Radhika SrinivasanDaniel Pelletier
Oct 4, 2005·Journal of Neuroimmunology·Kandace K FlemingJanet G Marquis
Oct 6, 2005·Glia·Carlos MatuteMaría-Victoria Sánchez-Gómez
Oct 6, 2005·European Journal of Immunology·Ciriana OrabonaUrsula Grohmann
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesca FallarinoPaolo Puccetti
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rodrigo PachecoRafael Franco
Apr 10, 2007·Nature Medicine·Ursula GrohmannPaolo Puccetti
Jun 6, 2007·European Journal of Immunology·Clemens NeufertMarkus F Neurath
Oct 11, 2007·Brain Pathology·Jia NewcombeTerence Smith
Jul 16, 2008·Acta Neurologica Scandinavica·S J KimD-U Jeong
Jan 1, 2009·Nature Reviews. Drug Discovery·P Jeffrey ConnCraig W Lindsley
May 16, 2009·Nature Reviews. Immunology·Joan Goverman
May 23, 2009·Nature Reviews. Immunology·Kevin J Tracey
May 26, 2009·Immunity·Liang ZhouDan R Littman
Jul 1, 2009·BMC Bioinformatics·Andrea BisogninStefania Bortoluzzi
Oct 14, 2009·The Journal of Experimental Medicine·Francesca FallarinoRiccardo Calafiore
Nov 21, 2009·Cell Death and Differentiation·D CentonzeG Martino
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Roopa BhatLawrence Steinman
Mar 3, 2010·Seminars in Immunopathology·Benjamin Matthew Segal
Mar 11, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alla L ZozulyaHeinz Wiendl

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Citations

Mar 28, 2013·Neurotoxicity Research·Arik EisenkraftArseny Finkelstein
Aug 2, 2011·Nature Immunology·Maria T PallottaUrsula Grohmann
Aug 7, 2010·Nature Medicine·Anna M Hansen, Rachel R Caspi
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daniel Hoyer
Jun 30, 2012·International Journal of Biological Sciences·Weizhen LuoLongchao Zhang
Mar 26, 2013·Neurodegenerative Disease Management·Jonathan W Dickerson, P Jeffrey Conn
Aug 26, 2014·Neurochemical Research·Marion S Mercier, David Lodge
Apr 9, 2014·Schizophrenia Bulletin·Monojit Debnath, Michael Berk
Aug 20, 2015·International Journal of Molecular Sciences·Cecilia RajdaLászló Vécsei
Dec 19, 2014·Expert Opinion on Investigational Drugs·Jacob Raber, Robert M Duvoisin
Mar 25, 2014·Experimental Neurology·Benjamin SchattlingManuel A Friese
Jan 1, 2013·Journal of Chemical Neuroanatomy·Cristina SanabraGuadalupe Mengod
Aug 13, 2014·European Journal of Immunology·Alessia ZosoLuca Inverardi
Jan 24, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Bing ZhuIndira Guleria
Nov 3, 2010·Neuropharmacology·F NicolettiJ P Pin
May 24, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Joshua M GammonChristopher M Jewell
Nov 15, 2013·Journal of Neurochemistry·Claire J Williams, David T Dexter
Oct 1, 2013·Neurobiology of Disease·Hilary Highfield Nickols, P Jeffrey Conn
Nov 6, 2012·European Journal of Pharmacology·Marcela Julio-PieperJohn F Cryan
Jan 3, 2014·Clinical & Developmental Immunology·Nathalie DeckxNathalie Cools
Apr 22, 2015·Nature Structural & Molecular Biology·Jelena VermezovicFabrizio d'Adda di Fagagna
May 30, 2012·Neuropharmacology·C VolpiF Fallarino
Feb 3, 2015·Frontiers in Cellular Neuroscience·Simona Federica SpampinatoMaria Angela Sortino
Feb 3, 2016·Molecular Nutrition & Food Research·Naveena B JanakiramChinthalapally V Rao
Jun 25, 2017·Journal of Biomedical Materials Research. Part a·Joshua M GammonChristopher M Jewell
Dec 28, 2017·International Journal of Molecular Sciences·Julia Fernández-MontoyaPilar Negredo
Mar 1, 2018·Expert Opinion on Drug Discovery·Claudia VolpiUrsula Grohmann
Jul 19, 2017·Cold Spring Harbor Perspectives in Biology·Juming YanMichele W L Teng
Sep 3, 2010·Nature Reviews. Drug Discovery·Katie Kingwell
Nov 30, 2018·Annual Review of Immunology·Craig N MorrellDenisse Vega Ocasio

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