DJ-1 depletion prevents immunoaging in T-cell compartments

Ni Zeng, Christophe M. Capelle (Main author), Alexandre Baron, Takumi Kobayashi, Severine Cire, Vera Tslaf, Cathy Leonard, Djalil Coowar, Haruhiko Koseki, Astrid M. Westendorf, Jan Buer, Dirk Brenner, Rejko Krüger, Rudi Balling, Markus Ollert, Feng Q. Hefeng*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson’s disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

Original languageEnglish
Pages (from-to)e53302
JournalEMBO Reports
Volume23
Issue number3
Early online date17 Jan 2022
DOIs
Publication statusPublished - 3 Feb 2022

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