Peripheral serotonin (5-hydroxytryptamine, 5HT) regulates cell growth and differentiation in numerous cell types through engagement of seven types of cell surface receptors (HTR1-7). Deregulated 5HT/HTR levels contribute to pathology in chronic inflammatory diseases, with macrophages being relevant targets for the physio-pathological effects of 5HT.
We have previously demonstrated that anti-inflammatory human macrophages are characterized by the specific expression of the serotonin receptors HTR2B and HTR7, and that 5HT skews human macrophage polarization through engagement of HTR2B and HTR7 receptors.
Currently we are addressing the role of 5HT in priming macrophages for reduced pro-inflammatory cytokine production and IFN type I-mediated signaling, and evaluating the receptor that mediates the anti-inflammatory and pro-fibrotic effect of serotonin on human macrophages. To that end we are using both in vitro macrophage generation systems as well as animal models of chronic inflammatory disease (arthritis, fibrosis) using strains of mice specifically defective in either Htr2b or Htr7.