Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi-mature tolerogenic dendritic cells

Authors

  • Sandrine Rullé,

    1. Sorbonne Paris Cité, Université Paris 13, Bobigny, France
    2. AP-HP Assistance Publique-Hôpitaux de Paris, GH Avicenne-Jean Verdier-René Muret, Service de Rhumatologie, Bobigny, France
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  • Marie-Dominique Ah Kioon,

    1. INSERM UMR-S, hôpital Lariboisière, Paris, France
    2. Paris-Diderot University, School of Medicine, Paris, France
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  • Carine Asensio,

    1. INSERM UMR-S, hôpital Lariboisière, Paris, France
    2. Paris-Diderot University, School of Medicine, Paris, France
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  • Julie Mussard,

    1. Sorbonne Paris Cité, Université Paris 13, Bobigny, France
    2. AP-HP Assistance Publique-Hôpitaux de Paris, GH Avicenne-Jean Verdier-René Muret, Service de Rhumatologie, Bobigny, France
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  • Hang-Korng Ea,

    1. INSERM UMR-S, hôpital Lariboisière, Paris, France
    2. Paris-Diderot University, School of Medicine, Paris, France
    3. Lariboisière Hospital, AP-HP, Paris, France
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  • Marie-Christophe Boissier,

    1. Sorbonne Paris Cité, Université Paris 13, Bobigny, France
    2. AP-HP Assistance Publique-Hôpitaux de Paris, GH Avicenne-Jean Verdier-René Muret, Service de Rhumatologie, Bobigny, France
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  • Frédéric Lioté,

    1. INSERM UMR-S, hôpital Lariboisière, Paris, France
    2. Paris-Diderot University, School of Medicine, Paris, France
    3. Lariboisière Hospital, AP-HP, Paris, France
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  • Géraldine Falgarone

    1. Sorbonne Paris Cité, Université Paris 13, Bobigny, France
    2. AP-HP Assistance Publique-Hôpitaux de Paris, GH Avicenne-Jean Verdier-René Muret, Service de Rhumatologie, Bobigny, France
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G. Falgarone, Li2P, EA 4222, Paris 13 University, AP-HP, Avicenne Hospital; Rheumatology Department, 125 route de Stalingrad, Bobigny 93009, France. Email: g.falgarone@avc.aphp.fr
Senior author: G. Falgarone

Summary

Dendritic cells (DC) play a pivotal role in tolerance. Adrenomedullin (AM), a neuropeptide with anti-apoptotic and anti-inflammatory effects, may decrease T helper type 1 effector cells and induce regulatory T (Treg) cells. The aim of this study was to evaluate AM effects on murine dendritic cell (DC) maturation and functions. Bone marrow-derived DC were produced and stimulated with CpG motifs, lipopolysaccharide or AM for 24 hr. Then, DC maturation and expression of AM and AM receptors were evaluated. Compared with lipopolysaccharide-stimulated or CpG-stimulated DC, AM-stimulated DC had lower levels of co-stimulatory molecule expression and pro-inflammatory cytokine release. The AM induced high levels of interferon-γ but not of interleukin-10. Importantly, AM inhibited lipopolysaccharide-induced maturation of DC. However, allogeneic T-cell stimulation and endocytic capacity of AM-stimulated DC were comparable to those of semi-mature and mature DC. Moreover, DC expressed AM and its receptors at a basal level, and AM receptor expression increased with DC maturation. The AM stimulation induced indoleamine 2,3-dioxygenase (IDO) expression, promoting Treg cell expansion. For the first time, we describe the DC maturation phenotype by a neuropeptide (AM). We have demonstrated that AM and its receptors are expressed in DC and that exogenous AM can modify the DC phenotype and functions and can induce a semi-mature DC phenotype with IDO expression. These results indicate close interactions among immune system regulation mechanisms and calcitonin-like peptides.

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