Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation

Proceedings of the National Academy of Sciences of the United States of America
Michihito KonoGeorge C Tsokos

Abstract

Th17 cells favor glycolytic metabolism, and pyruvate dehydrogenase (PDH) is the key bifurcation enzyme, which in its active dephosphorylated form advances the oxidative phosphorylation from glycolytic pathway. The transcriptional factor, inducible cAMP early repressor/cAMP response element modulator (ICER/CREM), has been shown to be induced in Th17 cells and to be overexpressed in CD4+ T cells from the patients with systemic lupus erythematosus (SLE). We found that glycolysis and lactate production in in vitro Th17-polarized T cells was reduced and that the expression of pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2), an enzyme that converts the inactive PDH to its active form, and PDH enzyme activity were increased in Th17 cells from ICER/CREM-deficient animals. ICER was found to bind to the Pdp2 promoter and suppress its expression. Furthermore, forced expression of PDP2 in CD4+ cells reduced the in vitro Th17 differentiation, whereas shRNA-based suppression of PDP2 expression increased in vitro Th17 differentiation and augmented experimental autoimmune encephalomyelitis. At the translational level, PDP2 expression was decreased in memory Th17 cells from patients with SLE and forced expression of PDP2 in CD4+ T...Continue Reading

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Citations

Dec 13, 2018·Current Opinion in Rheumatology·Florencia RosettiJosé C Crispín
Feb 17, 2019·Clinical and Experimental Immunology·X TengL Morel
Dec 17, 2019·Current Opinion in Rheumatology·Michihito KonoGeorge C Tsokos
Mar 13, 2020·Immunological Reviews·Xiangyu TengLaurence Morel
Aug 23, 2020·Current Opinion in Rheumatology·Jorge Romo-Tena, Mariana J Kaplan
Jan 24, 2019·Current Opinion in Rheumatology·Florencia RosettiJosé C Crispín
Jun 2, 2020·Immunometabolism·Bowen WuCornelia M Weyand
Apr 8, 2020·Immunometabolism·Milena VukelicGeorge C Tsokos
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Patrick C BradshawWilliam M Curtis
Jun 21, 2019·JCI Insight·Michihito KonoGeorge C Tsokos
Jan 18, 2020·Nature Reviews. Rheumatology·Amir Sharabi, George C Tsokos
Aug 31, 2019·Nature Communications·Cristina M LanataLindsey A Criswell
Dec 2, 2020·Nature Immunology·Cornelia M Weyand, Jörg J Goronzy
Nov 13, 2020·Clinical Reviews in Allergy & Immunology·Tingting WangXuan Zhang
Mar 12, 2021·Frontiers in Immunology·Michihito KonoGeorge C Tsokos
Apr 2, 2021·The FEBS Journal·Gina Papadopoulou, Georgina Xanthou
Apr 17, 2021·Environment International·Rongbin XuYuming Guo
Jun 13, 2021·Autoimmunity Reviews·Marc Scherlinger, George C Tsokos
Aug 28, 2021·Biological Chemistry·Sudheendra Hebbar Subramanyam, Klaus Tenbrock

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