title: 5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.
abstract: Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1) and 5-HTR(2) receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3), 5-HTR(4) and 5-HTR(7) receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.
authors: Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.
authors: Tobias
authors: T
authors: Müller
authors: Thorsten
authors: T
authors: Dürk
authors: Britta
authors: B
authors: Blumenthal
authors: Melanie
authors: M
authors: Grimm
authors: Sanja
authors: S
authors: Cicko
authors: Elisabeth
authors: E
authors: Panther
authors: Stephan
authors: S
authors: Sorichter
authors: Yared
authors: Y
authors: Herouy
authors: Francesco
authors: F
authors: Di Virgilio
authors: Davide
authors: D
authors: Ferrari
authors: Johannes
authors: J
authors: Norgauer
authors: Marco
authors: M
authors: Idzko
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D012701:Serotonin / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D012701:Serotonin