Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells

Serotonin is a monoamine neurotransmitter that signals through a wide array of receptors (5-HT(1–7)) many of which are also involved in immune processes. Dendritic cells (DCs) are crucial players in immune defense by bridging innate and adaptive immune responses via their vast repertoire of pattern recognition receptors and antigen-presenting capability. Although serotonin is known to influence immunity at many levels, cell type-specific expression and function of its receptors remains poorly understood. Here we aimed to study 5-HT(1–7) expression and function in CD1a(−) and CD1a(+) human monocyte-derived DCs (moDCs). We found that the 5-HT(2B) receptor-subtype is solely expressed by the inflammatory CD1a(+) moDC subset. Specific 5-HT(2B) activation potently inhibited TLR2, TLR3, and TLR7/8-induced proinflammatory cytokine and chemokine (TNF-α, IL-6, IL-8, IP-10, IL-12) but not type I interferon-β responses. 5-HT(2B) agonism also interfered with the polarization of CD1a(+) moDC-primed CD4(+) T cells towards inflammatory Th1 and Th17 effector lymphocytes. Here we report the subset-specific expression and immunomodulatory function of 5-HT(2B) in human moDCs. Our results expand the biological role of 5-HT(2B) which may act not only as a neurotransmitter receptor, but also as an important modulator of both innate and adaptive immune responses.