serotonin-mediated tuning of human helper t cell responsiveness to the chemokine cxcl12serotonin-mediated优化人类辅助t细胞的趋化因子cxcl12响应能力.pdfVIP

Serotonin-Mediated Tuning of Human Helper T Cell Responsiveness to the Chemokine CXCL12 1 ¤ ` ` 2 1 1 1,3 Elena Magrini * , Ildiko Szabo , Andrea Doni , Javier Cibella , Antonella Viola 1 Humanitas Clinical Institute IRCCS, Rozzano, Milan, Italy, 2 Department of Biology, University of Padua, Padua, Italy, 3 Department of Translational Medicine, University of Milan, Rozzano, Milan, Italy 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-HT3) is functionally expressed in human primary T cells. In addition, specific 5-HT3 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-HT3 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. ` Citation: Magrini E, Szabo I, Doni A, Cibella J, Viola A (2011) Serotonin-Mediated Tuning of Human Helper T Cell Responsiveness to the Chemokine CXCL12. PLoS ONE 6(8): e22482. doi:10.1371/journal.pone.0022482 Editor: Paul Proost, Rega Institute, University of Leuven, Belgium Received March 22, 2011; Accepted June 22, 2011; Publis