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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3860-3866. Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-05-1843. This Article Full Text (PDF) All Versions of this Article: 2005-05-1843v1 106/12/3860    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 Marteau, F. Articles by Communi, D. Search for Related Content PubMed PubMed Citation Articles by Marteau, F. Articles by Communi, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 6, 2005 Accepted August 2, 2005 Thrombospondin-1 and indoleamine 2,3-dioxygenase are major targets of extracellular ATP in human dendritic cells Frederic Marteau, Nathalie Suarez Gonzalez, David Communi, Michel Goldman, Jean-Marie Boeynaems, and Didier Communi* Institute of Interdisciplinary Research, IRIBHM, Universite Libre de Bruxelles, Brussels, Belgium Institute for Medical Immunology, IMI, Universite Libre de Bruxelles, Gosselies, Belgium Institute of Interdisciplinary Research, IRIBHM, Universite Libre de Bruxelles, Brussels, Belgium; Department of Medical Chemistry, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium * Corresponding author; email: communid{at}ulb.ac.be. Extracellular adenosine triphosphate affects the maturation of human monocyte-derived dendritic cells (DCs), mainly by inhibiting Th1 cytokines, promoting Th2 cytokines, and modulating the expression of costimulatory molecules. In this study, we report that ATP can induce immunosuppression through its action on DCs defining a new role for extracellular nucleotides. Microarray analysis of ATP-stimulated human DCs revealed inter alia a drastic up-regulation of two genes encoding mediators involved in immunosuppression: thrombospondin-1 (TSP-1) and indoleamine 2,3-dioxygenase (IDO). The release of TSP-1 by DCs in response to ATP was confirmed at the protein level by ELISA, immunodetection and mass spectrometry analysis and has an anti-proliferative effect on T CD4+ lymphocytes through TSP-1/CD47 interaction. Our pharmacological data support the involvement of P2Y11 receptor in this ATP-mediated TSP-1 secretion. We demonstrate also that ATP significantly potentiates the up-regulation of IDO - a negative regulator of T lymphocyte proliferation - and kynurenine production initiated by IFN- in human DCs. Thus, extracellular ATP released from damaged cells and previously considered as danger signal is also a potent regulator of mediators playing key roles in immune tolerance. Consequently nucleotides derivatives may be considered as useful tools for DC-based immunotherapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-C. Yen, C.-C. Lin, Y.-L. Chen, S.-S. Huang, H.-J. Yang, C.-P. Chang, H.-Y. Lei, and M.-D. Lai A Novel Cancer Therapy by Skin Delivery of Indoleamine 2,3-Dioxygenase siRNA Clin. Cancer Res., January 15, 2009; 15(2): 641 - 649. [Abstract] [Full Text] [PDF] A. Shin, T. Toy, S. Rothenfusser, N. Robson, J. Vorac, M. Dauer, M. Stuplich, S. Endres, J. Cebon, E. Maraskovsky, et al. 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