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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1010-1017. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-07-2903. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-07-2903v1 107/3/1010    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by O'Connell, P. J Articles by Ahern, G. P Search for Related Content PubMed PubMed Citation Articles by O'Connell, P. J Articles by Ahern, G. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 20, 2005 Accepted September 21, 2005 A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells Peta J O'Connell, Xiangbin Wang, Matilde Leon-Ponte, Corrie Griffiths, Sandeep C Pingle, and Gerard P Ahern* Robarts Research Institute, London, ON, Canada; Departments of Surgery, Microbiology and Immunology, University of Western Ontario, London, ON, Canada Department of Pharmacology, Georgetown University, Washington, DC, USA * Corresponding author; email: gpa3{at}georgetown.edu. Adaptive immunity is triggered at the immune synapse where peptide-MHC complexes and co-stimulatory molecules expressed by dendritic cells (DC) are physically presented to T cells. Here we describe transmission of the inflammatory monoamine serotonin (5-HT), between these cells. DC take-up 5-HT from the microenvironment and from activated T cells (that synthesize 5-HT)and this uptake is inhibited by the anti-depressant, fluoxetine. Expression of 5-HT transporters (SERT) is regulated by DC maturation, exposure to microbial stimuli and physical interactions with T cells. Significantly, 5-HT sequestered by DC is stored within LAMP-1+ vesicles and subsequently released via Ca2+-dependent exocytosis which was confirmed by amperometric recordings. In turn, extracellular 5-HT can reduce T cell levels of cAMP, a modulator of T cell activation. Thus, through the uptake of 5-HT at sites of inflammation, and from activated T cells, DC may shuttle 5-HT to naive T cells and thereby modulate T cell proliferation and differentiation. These data constitute the first direct measurement of triggered exocytosis by DC and reveal a new and rapid type of signaling that may be optimized by the intimate synaptic environment between DC and T cells. Moreover, these results highlight an important role for 5-HT signaling in immune function and the potential consequences of commonly used drugs which target 5-HT uptake and release. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Nakano, T. Higashi, R. Takagi, K. Hashimoto, Y. Tanaka, and S. Matsushita Dopamine released by dendritic cells polarizes Th2 differentiation Int. Immunol., June 1, 2009; 21(6): 645 - 654. [Abstract] [Full Text] [PDF] O. Bloom, J. J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman Spinophilin participates in information transfer at immunological synapses J. Cell Biol., June 6, 2008; 181(2): 203 - 211. [Abstract] [Full Text] [PDF] K. Nakamura, T. Sato, A. Ohashi, H. Tsurui, and H. Hasegawa Role of a Serotonin Precursor in Development of Gut Microvilli Am. J. Pathol., February 1, 2008; 172(2): 333 - 344. [Abstract] [Full Text] [PDF] M. Leon-Ponte,, G. P. Ahern, and P. J. O'Connell Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor Blood, April 15, 2007; 109(8): 3139 - 3146. [Abstract] [Full Text] [PDF] I. Cloez-Tayarani and J.-P. Changeux Nicotine and serotonin in immune regulation and inflammatory processes: a perspective J. Leukoc. Biol., March 1, 2007; 81(3): 599 - 606. [Abstract] [Full Text] [PDF] R. Pacheco, H. Oliva, J. M. Martinez-Navio, N. Climent, F. Ciruela, J. M. Gatell, T. Gallart, J. Mallol, C. Lluis, and R. Franco Glutamate Released by Dendritic Cells as a Novel Modulator of T Cell Activation J. Immunol., November 15, 2006; 177(10): 6695 - 6704. [Abstract] [Full Text] [PDF] E. J. Meredith, M. J. Holder, A. Rosen, A. D. Lee, M. J. S. Dyer, N. M. Barnes, and J. Gordon Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin's lymphoma PNAS, September 5, 2006; 103(36): 13485 - 13490. [Abstract] [Full Text] [PDF] M. Stolk, M. Leon-Ponte, M. Merrill, G. P. Ahern, and P. J. O'Connell IP3Rs are sufficient for dendritic cell Ca2+ signaling in the absence of RyR1 J. Leukoc. Biol., September 1, 2006; 80(3): 651 - 658. [Abstract] [Full Text] [PDF] S. Agaugue, L. Perrin-Cocon, F. Coutant, P. Andre, and V. Lotteau 1-Methyl-Tryptophan Can Interfere with TLR Signaling in Dendritic Cells Independently of IDO Activity J. Immunol., August 15, 2006; 177(4): 2061 - 2071. [Abstract] [Full Text] [PDF]

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