Carbon monoxide-treated dendritic cells decrease β1-integrin induction on CD8+ T cells and protect from type 1 diabetes

Authors

  • Thomas Simon,

    1. ONIRIS, UMR_A 707 IECM, Nantes, France
    2. INRA, Nantes, France
    3. Université Nantes Angers LeMans, Nantes, France
    Current affiliation:
    1. INSERM, UMR 1064, Nantes, France
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    • These authors contributed equally to this work.

  • Sylvie Pogu,

    1. ONIRIS, UMR_A 707 IECM, Nantes, France
    2. INRA, Nantes, France
    3. Université Nantes Angers LeMans, Nantes, France
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    • These authors contributed equally to this work.

  • Virginie Tardif,

    1. Université Nantes Angers LeMans, Nantes, France
    2. INSERM, UMR 1064, Nantes, France
    3. CHU Nantes, ITUN, Nantes, France
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    • These authors contributed equally to this work.

  • Kevin Rigaud,

    1. ONIRIS, UMR_A 707 IECM, Nantes, France
    2. INRA, Nantes, France
    3. Université Nantes Angers LeMans, Nantes, France
    4. INSERM, UMR 1064, Nantes, France
    5. CHU Nantes, ITUN, Nantes, France
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  • Séverine Rémy,

    1. Université Nantes Angers LeMans, Nantes, France
    2. INSERM, UMR 1064, Nantes, France
    3. CHU Nantes, ITUN, Nantes, France
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  • Eliane Piaggio,

    1. UPMC/CNRS, UMR7211, INSERM, U959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France
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  • Jean-Marie Bach,

    1. ONIRIS, UMR_A 707 IECM, Nantes, France
    2. INRA, Nantes, France
    3. Université Nantes Angers LeMans, Nantes, France
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  • Ignacio Anegon,

    1. Université Nantes Angers LeMans, Nantes, France
    2. INSERM, UMR 1064, Nantes, France
    3. CHU Nantes, ITUN, Nantes, France
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  • Philippe Blancou

    Corresponding author
    1. INRA, Nantes, France
    2. Université Nantes Angers LeMans, Nantes, France
    • ONIRIS, UMR_A 707 IECM, Nantes, France
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Full correspondence: Dr. Philippe Blancou, CHU Hotel Dieu, UMR INSERM 1064, 30 Boulevard Jean Monnet, Nantes F44093, France

Fax: +33-240-087-411

e-mail: philippe.blancou@gmail.com

Abstract

Carbon monoxide (CO) treatment improves pathogenic outcome of autoimmune diseases by promoting tolerance. However, the mechanism behind this protective tolerance is not yet defined. Here, we show in a transgenic mouse model for autoimmune diabetes that ex vivo gaseous CO (gCO)-treated DCs loaded with pancreatic β-cell peptides protect mice from disease. This protection is peptide-restricted, independent of IL-10 secretion by DCs and of CD4+ T cells. Although no differences were observed in autoreactive CD8+ T-cell function from gCO-treated versus untreated DC-immunized groups, gCO-treated DCs strongly inhibited accumulation of autoreactive CD8+ T cells in the pancreas. Interestingly, induction of β1-integrin was curtailed when CD8+ T cells were primed with gCO-treated DCs, and the capacity of these CD8+ T cells to lyse isolated islet was dramatically impaired. Thus, immunotherapy using CO-treated DCs appears to be an original strategy to control autoimmune disease.

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