5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.
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.
Müller
Tobias
T
Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.
Dürk
Thorsten
T
Blumenthal
Britta
B
Grimm
Melanie
M
Cicko
Sanja
S
Panther
Elisabeth
E
Sorichter
Stephan
S
Herouy
Yared
Y
Di Virgilio
Francesco
F
Ferrari
Davide
D
Norgauer
Johannes
J
Idzko
Marco
M
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*
D018925:Chemokines; D016207:Cytokines; D012701:Serotonin