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Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi‐mature tolerogenic dendritic cells
Author(s) -
Rullé Sandrine,
Kioon MarieDominique Ah,
Asensio Carine,
Mussard Julie,
Ea HangKorng,
Boissier MarieChristophe,
Lioté Frédéric,
Falgarone Géraldine
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2012.03577.x
Subject(s) - microbiology and biotechnology , receptor , dendritic cell , biology , lipopolysaccharide , adrenomedullin , immune system , cytokine , tlr9 , immunology , gene expression , biochemistry , dna methylation , gene
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.