5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo

• Published in: PloS one Vol. 4; no. 7; p. e6453
• Main Authors: Müller, Tobias, Dürk, Thorsten, Blumenthal, Britta, Grimm, Melanie, Cicko, Sanja, Panther, Elisabeth, Sorichter, Stephan, Herouy, Yared, Di Virgilio, Francesco, Ferrari, Davide, Norgauer, Johannes, Idzko, Marco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.07.2009; Public Library of Science (PLoS)
• Subjects: Adenosine; Airway management; Animals; Asthma; Biological properties; CCL22 protein; Cell Differentiation; Cell Movement - physiology; Cells, Cultured; Chemokines; Chemokines - metabolism; CXCL10 protein; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dermatology; Drainage; Gene expression; Hospitals; Humans; Immune response; Immune system; Immunology; Immunology/Allergy and Hypersensitivity; Immunology/Immune Response; Immunology/Innate Immunity; In vivo methods and tests; Inflammation; Inflammatory diseases; Interdisciplinary aspects; Interleukin 10; Interleukin 12; Interleukin 6; IP-10 protein; Leukocyte migration; Lipopolysaccharides; Lymph nodes; Lymph Nodes - cytology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Monocytes; Nervous system; Peripheral nervous system; Priming; Proteins; Receptor mechanisms; Receptors; Respiratory Medicine/Asthma; Rodents; Serotonin; Serotonin - physiology; T cell receptors; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Traffic control; Transgenic animals; Whooping cough; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006453

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.