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DJ‐1 depletion prevents immunoaging in T‐cell compartments
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892345/ https://www.ncbi.nlm.nih.gov/pubmed/35037711 http://dx.doi.org/10.15252/embr.202153302 |
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author | 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 |
author_facet | 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 |
author_sort | Zeng, Ni |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8892345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88923452022-03-15 DJ‐1 depletion prevents immunoaging in T‐cell compartments 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 EMBO Rep Reports 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. John Wiley and Sons Inc. 2022-01-17 2022-03-03 /pmc/articles/PMC8892345/ /pubmed/35037711 http://dx.doi.org/10.15252/embr.202153302 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reports 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 DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title | DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title_full | DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title_fullStr | DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title_full_unstemmed | DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title_short | DJ‐1 depletion prevents immunoaging in T‐cell compartments |
title_sort | dj‐1 depletion prevents immunoaging in t‐cell compartments |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892345/ https://www.ncbi.nlm.nih.gov/pubmed/35037711 http://dx.doi.org/10.15252/embr.202153302 |
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