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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3139-3146. Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-10-052787. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-052787v1 blood-2006-10-052787v2 109/8/3139    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 León-Ponte,, M. Articles by O'Connell, P. J. Search for Related Content PubMed PubMed Citation Articles by León-Ponte,, M. Articles by O'Connell, P. J. Related Collections Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor Matilde León-Ponte,1, Gerard P. Ahern4, and Peta J. O'Connell1,3 1 Robarts Research Institute, London, ON, Canada; 2 Department of Surgery and 3 Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada; 4 Department of Pharmacology, Georgetown University, Washington, DC Although typically considered a neurotransmitter, there is substantial evidence that serotonin (5-HT) plays an important role in the pathogenesis of inflammatory disorders. Despite these findings, the precise role of 5-HT in modulating immune function, particularly T-cell function, remains elusive. We report that naive T cells predominantly express the type 7 5-HT receptor (5-HTR), and expression of this protein is substantially enhanced on T-cell activation. In addition, T-cell activation leads to expression of the 5-HT1B and 5-HT2A receptors. Significantly, exogenous 5-HT induces rapid phosphorylation of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and IB in naive T cells. 5-HT–induced activation of ERK1/2 and NFB is inhibited by preincubation with a specific 5-HT7 receptor antagonist. Thus, 5-HT signaling via the 5-HT7 receptor may contribute to early T-cell activation. In turn, 5-HT synthesized by T cells may act as an autocrine factor. Consistent with this hypothesis, we found that inhibition of 5-HT synthesis with parachlorophenylalanine (PCPA) impairs T-cell activation and proliferation. Combined, these data demonstrate a fundamental role for 5-HT as an intrinsic cofactor in T-cell activation and function and suggest an alternative mechanism through which immune function may be regulated by indoleamine 2,3-dioxygenase–mediated catabolism of tryptophan. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Serotonin: a real blast for T cells John Gordon and Nicholas M. Barnes Blood 2007 109: 3130-3131. [Full Text] [PDF] This article has been cited by other articles: A Kling, M Seddighzadeh, L Arlestig, L Alfredsson, S Rantapaa-Dahlqvist, and L Padyukov Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis Ann Rheum Dis, August 1, 2008; 67(8): 1111 - 1115. [Abstract] [Full Text] [PDF]

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