Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity.

The Journal of Experimental Medicine
Shannon E DunnLawrence Steinman

Abstract

Peroxisome proliferator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-gamma(+)IL-17A(-) and IFN-gamma(+)IL-17A(+) CD4(+) cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constellation of immune system aberrations that included higher CD4(+) cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune ...Continue Reading

References

Oct 1, 1995·Molecular and Cellular Biology·T L MurphyK M Murphy
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M FormanR M Evans
Jan 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ajay ChawlaRonald M Evans
Jun 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dallas C JonesRaymond A Daynes
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy E Lovett-RackeMichael K Racke
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Feb 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Francisco J SchopferBruce A Freeman
Nov 6, 2007·Trends in Immunology·Daniel S Straus, Christopher K Glass
Feb 19, 2008·Nature Medicine·Ingunn M StromnesJoan M Goverman
Oct 7, 2008·Current Opinion in Immunology·Caroline DiveuDaniel J Cua
Jan 31, 2009·Immunology·Thomas M AuneShaojing Chang
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne R GockeMichael K Racke
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amit AwasthiMohamed Oukka
Jun 24, 2009·The Journal of Experimental Medicine·Yuhong YangAmy E Lovett-Racke
Oct 8, 2009·Annals of Neurology·Hania KebirAlexandre Prat

❮ Previous
Next ❯

Citations

Mar 3, 2012·Molecules and Cells·Je-Min Choi, Alfred L M Bothwell
Jan 15, 2011·PPAR Research·Yuhong YangMichael K Racke
Dec 29, 2010·Autoimmune Diseases·Kemal Ugur TufekciKursad Genc
Jan 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Peggy P Ho, Lawrence Steinman
Jul 12, 2011·Expert Opinion on Therapeutic Targets·Emanuela Esposito, Salvatore Cuzzocrea
Jan 22, 2015·The Journal of Clinical Investigation·James T WalshJonathan Kipnis
Dec 2, 2014·Pharmacology & Therapeutics·Katja SchmitzIrmgard Tegeder
Sep 30, 2016·Scientific Reports·Isabelle Mothe-SatneyJaap G Neels
Aug 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Marie LiebmannLuisa Klotz
Jul 13, 2011·FEBS Letters·L Klotz, P Knolle
Sep 28, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fei Linda ZhaoShannon E Dunn
Sep 26, 2012·Nature Reviews. Immunology·Marc Veldhoen, Verena Brucklacher-Waldert
Oct 2, 2014·EMBO Molecular Medicine·Katja SchmitzIrmgard Tegeder
Jul 6, 2014·Physiological Reviews·Jaap G Neels, Paul A Grimaldi
Oct 4, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paulina C DrohomyreckyShannon E Dunn
May 5, 2020·Journal of Cellular and Molecular Medicine·Yan ShiQing Tian
Aug 5, 2017·Experimental & Molecular Medicine·Hong-Jai Park, Je-Min Choi
Jun 6, 2018·International Journal of Molecular Sciences·Véronique Ferret-SenaArmando Sena
May 13, 2020·PPAR Research·Laurits J HolmKarsten Buschard
May 8, 2020·Cells·Nicole Wagner, Kay-Dietrich Wagner
Oct 31, 2018·International Journal of Molecular Sciences·Yi LiuImad Shureiqi
Aug 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hajime TakeuchiMakoto Iwata
May 26, 2018·International Journal of Molecular Sciences·Gwenaëlle Le Menn, Jaap G Neels

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR
PMA
transfection

Software Mentioned

FlowJo

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.