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DJ‐1 depletion prevents immunoaging in T‐cell compartments
Authors:Ni Zeng  Christophe M Capelle  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
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.
Keywords:aging  CD8 T cells  immune aging  immunosenescence  PARK7/DJ‐  1
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