Reference : DJ‐1 depletion prevents immunoaging in T‐cell compartments.
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/54385
DJ‐1 depletion prevents immunoaging in T‐cell compartments.
English
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]
* These authors have contributed equally to this work.
[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.
[Luxembourg Institute of Health - LIH > Department of Infection and Immunity > > ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM)]
