title: Serotonin activates dendritic cell function in the context of gut inflammation.
abstract: Mucosal inflammation in the gut is characterized by infiltration of innate and adaptive immune cells and by an alteration in serotonin-producing enterochromaffin cells. We investigated the role of serotonin in the function of dendritic cells (DCs) and sequential T-cell activation in relation to generation of gut inflammation. DCs isolated from tryptophan hydroxylase-1-deficient (TPH1(-/-)) mice, which have reduced serotonin in the gut, and wild-type (TPH1(+/+)) mice with or without dextran sulfate sodium (DSS)-induced colitis were stimulated with lipopolysaccharide to assess interleukin-12 (IL-12) production. Isolated DCs from TPH1(+/+) and TPH1(-/-) mice were also cocultured with CD4(+) T cells of naive TPH1(+/+) mice to assess the role of serotonin in priming T cells. In addition, serotonin-pulsed DCs were transferred to TPH1(-/-) mice to assess the effect on DSS-induced colitis. Consistent with a reduced severity of colitis, DCs from DSS-induced TPH1(-/-) mice produced less IL-12 compared with the TPH1(+/+) mice. In vitro serotonin stimulation restored the cytokine production from TPH1(-/-) DCs and adoptive transfer of serotonin-pulsed DCs into TPH1(-/-) up-regulated colitis. Furthermore, CD4(+) T cells primed by TPH1(-/-) DCs produce reduced the levels of IL-17 and interferon-γ. This study provides novel information on serotonin-mediated immune signaling and promotion of interactions between innate and adaptive immune responses in the context of gut inflammation, which may ultimately lead to improved strategies to combat gut inflammatory disorders.
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.forename: Jessica
authors.initials: J
authors.lastname: McClemens
authors.forename: Francine
authors.initials: F
authors.lastname: Cote
authors.forename: Youko
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D045142:Cross-Priming / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D016264:Dextran Sulfate; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012701:Serotonin; D016264:Dextran Sulfate