[en] 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.
Disciplines :
Sciences du vivant: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Zeng, Ni ✱; Luxembourg Institute of Health - LIH > Department of Infection and Immunity ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM)
Capelle, Christophe M. ✱; Luxembourg Institute of Health - LIH > Department of Infection and Immunity ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM)
BARON, Alexandre ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
KOBAYASHI, Takumi ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
Cire, Severine; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
TSLAF, Vera ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) ; Luxembourg Institute of Health - LIH > Transversal Translational Medicine
Leonard, Cathy; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
COOWAR, Djalil ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services
Koseki, Haruhiko; RIKEN Center for Integrative Medical Sciences > Laboratory for Developmental Genetics ; Japanese Agency for Medical Research and Development > AMED-CREST
Westendorf, Astrid M.; University Duisburg-Essen, University Hospital Essen > Institute of Medical Microbiology
Buer, Jan; University Duisburg-Essen, University Hospital Essen > Institute of Medical Microbiology
BRENNER, Dirk ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity
KRÜGER, Rejko ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience ; Luxembourg Institute of Health - LIH > Transversal Translational Medicine ; Centre Hospitalier de Luxembourg - CHL
Balling, Rudi; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
OLLERT, Markus ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity ; University of Southern Denmark, Odense Research Center for Anaphylaxis - ORCA > Department of Dermatology and Allergy Center
HE, Feng ; Luxembourg Institute of Health - LIH > Department of Infection and Immunity ; University Duisburg-Essen, University Hospital Essen > Institute of Medical Microbiology
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