Mesenchymal Stem Cells Inhibit the Differentiation of Dendritic Cells Through an Interleukin-6-Dependent Mechanism

Authors

  • Farida Djouad,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Louis-Marie Charbonnier,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Carine Bouffi,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Pascale Louis-Plence,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Claire Bony,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Florence Apparailly,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Céline Cantos,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
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  • Christian Jorgensen,

    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
    3. Centre Hospitalier Universitaire Montpellier, Hôpital Lapeyronie, Unité Clinique d'Immuno-Rhumatologie, Montpellier, France
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  • Danièle Noël Ph.D.

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, U 844, Montpellier, France
    2. Université Montpellier, Unité de Formation et de Recherche de Médecine, Montpellier, France
    • Institut National de la Santé et de la Recherche Médicale, U 844, Hôpital Saint-Eloi, Bât INM, 80 Avenue Augustin Fliche, F-34091 Montpellier, France. Telephone: 33 (0) 4 99 63 60 26; Fax: 33 (0) 4 99 63 60 20
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Abstract

Mesenchymal stem cells (MSC) are of particular interest for their potential clinical use in tissue engineering as well as for their capacity to reduce the incidence and severity of graft-versus-host disease in allogeneic transplantation. We have previously shown that MSC-mediated immune suppression acts via the secretion of soluble factor(s) induced upon stimulation. The aim of this study was to identify the molecule(s) involved and the underlying mechanism(s). We show that murine MSC secrete high levels of interleukin (IL)-6 and vascular endothelial growth factor, which are directly correlated to the inhibition of T-cell proliferation. The T-cell activation is partially restored upon addition of a neutralizing anti-IL-6 antibody or the prostaglandin E2 inhibitor indomethacin. Interestingly, no indoleamine 2,3-dioxygenase activity was detected in our conditions. Instead, we show that MSC reduce the expression of major histocompatibility complex class II, CD40, and CD86 costimulatory molecules on mature dendritic cells (DC), which was responsible for a decrease in T-cell proliferation. Moreover, we show that the differentiation of bone marrow progenitors into DC cultured with conditioned supernatants from MSC was partly inhibited through the secretion of IL-6. Altogether, these data suggest that IL-6 is involved in the immunoregulatory mechanism mediated by MSC through a partial inhibition of DC differentiation but is probably not the main mechanism.

Disclosure of potential conflicts of interest is found at the end of this article.

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