| Literature DB >> 35618940 |
Egle Danileviciute1,2,3, Ni Zeng1,3, Christophe M Capelle1,3, Nicole Paczia2, Mark A Gillespie4, Henry Kurniawan1, Mohaned Benzarti3,5, Myriam P Merz1,3, Djalil Coowar2, Sabrina Fritah6, Daniela Maria Vogt Weisenhorn7,8, Gemma Gomez Giro2, Melanie Grusdat1, Alexandre Baron1, Coralie Guerin1, Davide G Franchina1,3, Cathy Léonard1, Olivia Domingues1, Sylvie Delhalle1, Wolfgang Wurst7,8,9,10, Jonathan D Turner1, Jens Christian Schwamborn2, Johannes Meiser5, Rejko Krüger2,11,12, Jeff Ranish4, Dirk Brenner1,2,13, Carole L Linster2, Rudi Balling2,14, Markus Ollert1,13, Feng Q Hefeng15,16,17.
Abstract
Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson's disease gene) is a pacemaker regulating PDH activity in CD4+ regulatory T cells (Treg cells). DJ-1 binds to PDHE1-β (PDHB), inhibiting phosphorylation of PDHE1-α (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Park7 (Dj-1) deletion impairs Treg survival starting in young mice and reduces Treg homeostatic proliferation and cellularity only in aged mice. This leads to increased severity in aged mice during the remission of experimental autoimmune encephalomyelitis (EAE). Dj-1 deletion also compromises differentiation of inducible Treg cells especially in aged mice, and the impairment occurs via regulation of PDHB. These findings provide unforeseen insight into the complicated regulatory machinery of the PDH complex. As Treg homeostasis is dysregulated in many complex diseases, the DJ-1-PDHB axis represents a potential target to maintain or re-establish Treg homeostasis.Entities:
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Year: 2022 PMID： 35618940 DOI： 10.1038/s42255-022-00576-y
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812