title: Serotonin-mediated tuning of human helper T cell responsiveness to the chemokine CXCL12.
abstract: In addition to its role as neurotransmitter, serotonin (5-HT) is an important modulator of inflammation and immunity. Here, we report novel findings suggesting a 5-HT involvement in T cell migration. In particular, we show that 5-HT tunes the responsiveness of human T lymphocytes to the broadly expressed chemokine CXCL12 in transwell migration assays. By real-time PCR, western blot analysis and electrophysiological patch clamp experiments, we demonstrate that the type 3 5-HT receptor (5-HT(3)) is functionally expressed in human primary T cells. In addition, specific 5-HT(3) receptor agonists selectively decrease T cell migration towards gradients of CXCL12 but not of inflammatory chemokines, such as CCL2 and CCL5. In transmigration experiments, 5-HT(3) receptor stimulation reverts the inhibitory effect of endothelial-bound CXCL12 on T cell migration. Our data suggest that the reduced T cell responsiveness to CXCL12 induced by 5-HT may occur to facilitate T cell extravasation and migration into inflamed tissues.
authors.affiliation: Humanitas Clinical Institute IRCCS, Rozzano, Milan, Italy. elena.magrini@ifom-ieo-campus.it
authors.forename: Elena
authors.initials: E
authors.lastname: Magrini
authors.forename: Ildikò
authors.initials: I
authors.lastname: Szabò
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Javier
authors.initials: J
authors.lastname: Cibella
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D058105:Polymerization / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects
chemical_list: D000199:Actins; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D011985:Receptors, Serotonin; D012701:Serotonin