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DJ‐1 depletion prevents immunoaging in T‐cell compartments
Author(s) -
Zeng Ni,
Capelle Christophe M,
Baron Alexandre,
Kobayashi Takumi,
Cire Severine,
Tslaf Vera,
Leonard Cathy,
Coowar Djalil,
Koseki Haruhiko,
Westendorf Astrid M,
Buer Jan,
Brenner Dirk,
Krüger Rejko,
Balling Rudi,
Ollert Markus,
Hefeng Feng Q
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202153302
Subject(s) - biology , cd8 , t cell , oxidative phosphorylation , microbiology and biotechnology , ageing , immune system , knockout mouse , immunology , genetics , gene , biochemistry
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.