title: The serotonin receptor 5-HT₇R regulates the morphology and migratory properties of dendritic cells.
abstract: Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7R) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7R, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7R was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7R enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7R-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7R could be a new target for treatment of a variety of inflammatory and immune disorders.
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Holst
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover 30625, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Schindler
authors.affiliation: Institute of Science and Technology Austria, Klosterneuburg 3400, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover 30625, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Himpriya
authors.initials: H
authors.lastname: Chopra
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover 30625, Germany Institute of Molecular Medicine, RWTH Aachen University, Aachen 52074, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover 30625, Germany Ponimaskin.Evgeni@mh-hannover.de.
authors.forename: Evgeni
authors.initials: E
authors.lastname: Ponimaskin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D054415:Chemokine CCL19 / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; C581598:Cdc42 protein, mouse; D054415:Chemokine CCL19; D012333:RNA, Messenger; D054400:Receptors, CCR7; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D020764:cdc42 GTP-Binding Protein
keywords: 5-HT7 receptor; Cdc42; Dendritic cell; Migration