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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2887-2893. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-06-027862. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-06-027862v1 109/7/2887    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 Aksoy, E. Articles by Goriely, S. Search for Related Content PubMed PubMed Citation Articles by Aksoy, E. Articles by Goriely, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells Ezra Aksoy1, Valentina Albarani1, Muriel Nguyen1, Jean-Francois Laes2, Jean-Louis Ruelle3, Dominique De Wit1, Fabienne Willems1, Michel Goldman1, and Stanislas Goriely1 1 Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Charleroi, Belgium; 2 Biovallée, Charleroi, Belgium; 3 GlaxoSmithKline Biologicals, Research and Development, Rixensart, Belgium The synthesis of interferon-ß (IFNß) and IFN-inducible factors elicited by lipopolysaccharide (LPS) depends on the transcriptional activity of interferon regulatory factor 3 (IRF-3) downstream of Toll-like receptor-4 (TLR4). To examine the ability of human newborns to mount TLR4-mediated IRF-3–dependent responses, we analyzed the pattern of genes expressed on the addition of LPS to cord blood or cord blood monocyte-derived dendritic cells (moDCs). Expression of IFNß and IFN-inducible genes was selectively impaired in neonatal blood and moDCs as compared with their adult counterparts. This selective defect was confirmed by microarray experiments on moDCs. Altered expression of IFN-inducible genes was related to impaired IFNß synthesis because IFNß signaling was functional in neonatal moDCs. However, addition of exogenous IFNß failed to restore LPS-induced IL-12p70 synthesis which was previously shown to be defective in neonatal moDCs. Although LPS-induced IRF-3 nuclear translocation was observed both in adult and neonatal moDCs, IRF-3 DNA-binding activity and association with the coactivator CREB-binding protein (CBP) were decreased in neonatal as compared with adult moDCs. We conclude that impaired IRF-3/CBP interaction in neonatal blood cells exposed to LPS is associated with impaired expression of IFNß and IFN-inducible genes. Because IRF-3 activity is also required for IL-12p70 synthesis, our findings provide a molecular basis for the decreased ability of LPS-stimulated neonatal moDCs to elicit Th1-type responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Brave new world: birth of immunity Robert Bortolussi Blood 2007 109: 2675-2676. [Full Text] [PDF] This article has been cited by other articles: T. R. Kollmann, J. Crabtree, A. Rein-Weston, D. Blimkie, F. Thommai, X. Y. Wang, P. M. Lavoie, J. Furlong, E. S. Fortuno III, A. M. Hajjar, et al. Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults J. Immunol., December 1, 2009; 183(11): 7150 - 7160. [Abstract] [Full Text] [PDF] I. Szatmari, D. Torocsik, M. Agostini, T. Nagy, M. Gurnell, E. Barta, K. Chatterjee, and L. Nagy PPAR{gamma} regulates the function of human dendritic cells primarily by altering lipid metabolism Blood, November 1, 2007; 110(9): 3271 - 3280. [Abstract] [Full Text] [PDF]

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