Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice
Abstract Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins i...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45984-8 |
| _version_ | 1827326830704590848 |
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| author | Aurélie Durand Nelly Bonilla Théo Level Zoé Ginestet Amélie Lombès Vincent Guichard Mathieu Germain Sébastien Jacques Franck Letourneur Marcio Do Cruzeiro Carmen Marchiol Gilles Renault Morgane Le Gall Céline Charvet Agnès Le Bon Bruno Martin Cédric Auffray Bruno Lucas |
| author_facet | Aurélie Durand Nelly Bonilla Théo Level Zoé Ginestet Amélie Lombès Vincent Guichard Mathieu Germain Sébastien Jacques Franck Letourneur Marcio Do Cruzeiro Carmen Marchiol Gilles Renault Morgane Le Gall Céline Charvet Agnès Le Bon Bruno Martin Cédric Auffray Bruno Lucas |
| author_sort | Aurélie Durand |
| collection | DOAJ |
| description | Abstract Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice. |
| first_indexed | 2024-03-07T14:51:11Z |
| format | Article |
| id | doaj.art-1522e57409074b918800d251389fd226 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:11Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1522e57409074b918800d251389fd2262024-03-05T19:39:52ZengNature PortfolioNature Communications2041-17232024-02-0115111910.1038/s41467-024-45984-8Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in miceAurélie Durand0Nelly Bonilla1Théo Level2Zoé Ginestet3Amélie Lombès4Vincent Guichard5Mathieu Germain6Sébastien Jacques7Franck Letourneur8Marcio Do Cruzeiro9Carmen Marchiol10Gilles Renault11Morgane Le Gall12Céline Charvet13Agnès Le Bon14Bruno Martin15Cédric Auffray16Bruno Lucas17Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016Abstract Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice.https://doi.org/10.1038/s41467-024-45984-8 |
| spellingShingle | Aurélie Durand Nelly Bonilla Théo Level Zoé Ginestet Amélie Lombès Vincent Guichard Mathieu Germain Sébastien Jacques Franck Letourneur Marcio Do Cruzeiro Carmen Marchiol Gilles Renault Morgane Le Gall Céline Charvet Agnès Le Bon Bruno Martin Cédric Auffray Bruno Lucas Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice Nature Communications |
| title | Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice |
| title_full | Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice |
| title_fullStr | Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice |
| title_full_unstemmed | Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice |
| title_short | Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice |
| title_sort | type 1 interferons and foxo1 down regulation play a key role in age related t cell exhaustion in mice |
| url | https://doi.org/10.1038/s41467-024-45984-8 |
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