Critical Role of P2Y12 Receptor in Regulation of Th17 Differentiation and Experimental Autoimmune Encephalomyelitis Pathogenesis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Chaoyan QinChangsheng Du

Abstract

Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to be associated with inflammation, but its function in T cell differentiation and autoimmune diseases pathogenesis is unclear. In this study, we found that the P2Y12 receptor was upregulated in the peripheral immune tissues of experimental autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced peak severity and cumulative disease score in EAE mice, followed by a dramatic reduction of leukocyte infiltration and less extensive demyelination. The percentage of Th17, one of the main pathogenic T cells in EAE, was sharply decreased in P2Y12 knockout mice, accompanied by decreased IL-17A production and a low mRNA level of Th17-related genes. In vitro culture assay further verified that P2Y12 directly regulated Th17 differentiation. More interestingly, clopidogrel and ticagrelor, two P2Y12-specific antagonists, effectively alleviated the disease severity of EAE and inhibited Th17 differentiation both in vivo and in vitro. Further study demonstrated that blocking the P2Y12 receptor also ameliorated the symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced co...Continue Reading

References

Mar 1, 1997·Trends in Pharmacological Sciences·B B FredholmM Williams
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·J Jin, S P Kunapuli
Feb 7, 2001·BMJ : British Medical Journal·R MilneJ Bryant
Sep 8, 2001·The Journal of Biological Chemistry·D CommuniJ M Boeynaems
Apr 17, 2002·Lancet·Alastair Compston, Alasdair Coles
Oct 9, 2002·Journal of Autoimmunity·Sung-E ChoiYup Kang
Feb 1, 2003·Trends in Pharmacological Sciences·Maria P AbbracchioGeoffrey Burnstock
Oct 7, 2003·Nature Medicine·Alexandra MoersStefan Offermanns
Dec 12, 2003·Hematology·Robert T DorsamSatya P Kunapuli
Nov 18, 2004·Immunological Reviews·Claire L LangrishDaniel J Cua
May 13, 2005·International Journal of Immunopathology and Pharmacology·P BalleriniU Traversa
Jul 6, 2005·British Journal of Pharmacology·Michelle Scrivens, John M Dickenson
Oct 4, 2006·Neuron·Stephen L Hauser, Jorge R Oksenberg
Nov 23, 2006·Nature Neuroscience·Sharon E HaynesDavid Julius
Dec 16, 2006·Nature Reviews. Immunology·Ken Shortman, Shalin H Naik
Sep 19, 2008·Immunity·David AlvarezUlrich H von Andrian
Mar 18, 2009·Diabetes·Juliet A EmamaulleeA M James Shapiro
May 12, 2009·Biochemical and Biophysical Research Communications·Mitsutoshi TsukimotoShuji Kojima
Oct 14, 2009·The Journal of Experimental Medicine·Sailaja ParuchuriJoshua A Boyce
Nov 10, 2009·Biochemical Pharmacology·Zhan-Guo GaoKenneth A Jacobson
Nov 28, 2009·Basic Research in Cardiology·Philipp DiehlMartin Moser
Dec 19, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kees Jalink, Wouter H Moolenaar
Feb 9, 2010·Expert Review of Cardiovascular Therapy·Davide CapodannoDominick J Angiolillo
Oct 19, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Abduelhakem Ben AddiBernard Robaye
Nov 26, 2010·Molecular and Cellular Endocrinology·Amanda Jabin GustafssonMd Shahidul Islam
Jan 15, 2011·Platelets·Soochong Kim, Satya P Kunapuli
Jun 6, 2012·Cell Research·Changsheng Du, Xin Xie
Oct 4, 2012·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Yu JinChangqing Zheng
Apr 16, 2013·Trends in Molecular Medicine·Aiden HaghikiaLars Fugger
Dec 3, 2013·Rinshō shinkeigaku = Clinical neurology·Makoto Matsui
Sep 3, 2014·Mediators of Inflammation·Susanna AmadioCinzia Volonté
Nov 21, 2015·European Journal of Medicinal Chemistry·Ivan B YanachkovAndrew L Frelinger
Feb 20, 2016·Immunologic Research·Inna TabanskyJoel N H Stern
Mar 14, 2016·International Immunopharmacology·Su-Min LimDong-Hyun Kim

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Dec 7, 2019·Journal of Cell Communication and Signaling·Harika VemulapalliElisabetta Liverani
Jun 4, 2018·Acta Biochimica Et Biophysica Sinica·Jinjin WangZhugang Wang
Sep 29, 2019·Nature Reviews. Immunology·Tao GongRongbin Zhou
Oct 31, 2020·Frontiers in Immunology·Elias RawishHarald F Langer
Oct 8, 2021·Nature Communications·Yuki FujiwaraYuwen Zhu

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