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Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice

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  • Aurélie Durand

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Nelly Bonilla

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Théo Level

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Zoé Ginestet

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Amélie Lombès

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Vincent Guichard

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Mathieu Germain

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Sébastien Jacques

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Franck Letourneur

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Marcio Cruzeiro

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Carmen Marchiol

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Gilles Renault

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Morgane Gall

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Céline Charvet

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
    CNRS UMR7104
    INSERM U1258
    Université de Strasbourg)

  • Agnès Bon

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Bruno Martin

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Cédric Auffray

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

  • Bruno Lucas

    (Université Paris-Cité, Institut Cochin, Centre National de la Recherche Scientifique (CNRS) UMR8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U1016)

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.

Suggested Citation

  • Aurélie Durand & Nelly Bonilla & Théo Level & Zoé Ginestet & Amélie Lombès & Vincent Guichard & Mathieu Germain & Sébastien Jacques & Franck Letourneur & Marcio Cruzeiro & Carmen Marchiol & Gilles Ren, 2024. "Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45984-8
    DOI: 10.1038/s41467-024-45984-8
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    References listed on IDEAS

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