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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3696-3703. Prepublished online as a Blood First Edition Paper on August 12, 2008; DOI 10.1182/blood-2008-05-155408. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-05-155408v1 112/9/3696    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 Chizzolini, C. Articles by Dayer, J.-M. Search for Related Content PubMed PubMed Citation Articles by Chizzolini, C. Articles by Dayer, J.-M. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion Carlo Chizzolini1, Rachel Chicheportiche1, Montserrat Alvarez1, Casimir de Rham1, Pascale Roux-Lombard1, Sylvie Ferrari-Lacraz1, and Jean-Michel Dayer1 1 Division of Immunology and Allergy, Department of Internal Medicine, University Hospital and School of Medicine, Geneva, Switzerland Microenvironment molecular cues direct T helper (Th) cell differentiation; however, Th17 fate determination is still imprecisely understood in humans. To assess the role of prostaglandin E2 (PGE2) in Th expansion, we activated peripheral blood mononuclear cells by CD3 cross-linking. In the presence of exogenous PGE2, peripheral blood mononuclear cells produced higher interleukin-17 (IL-17), C-C chemokine ligand 20 (CCL20)/macrophage inflammatory protein 3 (MIP-3), CXC chemokine ligand 8 (CXCL8)/IL-8, and lower interferon- and IL-22 levels than in control cultures. Exogenous PGE2 and IL-23 synergized in inducing IL-17, whereas indomethacin and IL-23 blockade drastically reduced IL-17 but not interferon- production. Furthermore, IL-1 but not tumor necrosis factor was absolutely required for IL-17 production. PGE2 doubled the frequency of CD4+ T cells producing IL-17 and within the CD4+ subset enhanced C-C chemokine receptor 6 (CCR6) and CCR4 while decreasing CXC chemokine receptor 3 (CXCR3) expression. Furthermore, in CD4+ T-cell lines, the production of IL-17 segregated with the CCR6+ subset. In the presence of CCR6+ compared with CXCR3+ Th cells, monocytes/macrophages produced much higher levels of matrix metalloproteinase-1, -3, and -9 but similar levels of CXCL10 and IL-1β. These results identify PGE2 and IL-23 as participating in the expansion of CD4+ T cells endowed with high IL-17 production capacity, which in turn favors monocyte production of mediators important for host defense and tissue destruction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. A. Blaho, M. W. Buczynski, E. A. Dennis, and C. R. Brown Cyclooxygenase-1 Orchestrates Germinal Center Formation and Antibody Class-Switch via Regulation of IL-17 J. Immunol., November 1, 2009; 183(9): 5644 - 5653. [Abstract] [Full Text] [PDF] J.-M. Dayer and E. Choy Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor Rheumatology, October 23, 2009; (2009) kep329v1. [Abstract] [Full Text] [PDF] G. Murugaiyan and B. 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Fernandez The Induction of IL-10 by Zymosan in Dendritic Cells Depends on CREB Activation by the Coactivators CREB-Binding Protein and TORC2 and Autocrine PGE2 J. Immunol., July 15, 2009; 183(2): 1471 - 1479. [Abstract] [Full Text] [PDF] H. P. Lemos, R. Grespan, S. M. Vieira, T. M. Cunha, W. A. Verri Jr., K. S. S. Fernandes, F. O. Souto, I. B. McInnes, S. H. Ferreira, F. Y. Liew, et al. Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFN{gamma} production PNAS, April 7, 2009; 106(14): 5954 - 5959. [Abstract] [Full Text] [PDF] K. Boniface, K. S. Bak-Jensen, Y. Li, W. M. Blumenschein, M. J. McGeachy, T. K. McClanahan, B. S. McKenzie, R. A. Kastelein, D. J. Cua, and R. de Waal Malefyt Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling J. Exp. Med., March 16, 2009; 206(3): 535 - 548. [Abstract] [Full Text] [PDF]

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