title: Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi-mature tolerogenic dendritic cells.
abstract: 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.
authors.affiliation: Sorbonne Paris Cité, Université Paris 13, Bobigny, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rullé
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Ah Kioon
authors.forename: Carine
authors.initials: C
authors.lastname: Asensio
authors.forename: Julie
authors.initials: J
authors.lastname: Mussard
authors.forename: Hang-Korng
authors.initials: HK
authors.lastname: Ea
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lioté
authors.forename: Géraldine
authors.initials: G
authors.lastname: Falgarone
mesh_terms: D053607:Adrenomedullin / Q000096:biosynthesis / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D058265:Receptors, Adrenomedullin / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D058265:Receptors, Adrenomedullin; D016753:Interleukin-10; D053607:Adrenomedullin; D007371:Interferon-gamma