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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1113-1122. Prepublished online as a Blood First Edition Paper on October 3, 2006; DOI 10.1182/blood-2006-05-023465. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-023465v1 109/3/1113    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 Longman, R. S. Articles by Albert, M. L. Search for Related Content PubMed PubMed Citation Articles by Longman, R. S. Articles by Albert, M. L. Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-/ß on antigen cross-presentation Randy S. Longman1,2,3, Deborah Braun3, Sandra Pellegrini3, Charles M. Rice1, Robert B. Darnell1, and Matthew L. Albert3,4 From the1 Rockefeller University, New York, NY; 2 Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY; 3 Institut Pasteur, Paris, France; and 4 Institut National de la Santé et de la Recherche Médicale (INSERM) AV0201, Paris, France The broad and often contrasting effects of type I interferons (IFNs) in innate and adaptive immunity are belied by the signaling via a single receptor, IFN- receptor (IFNAR). Here, we show that IFN-/ß induces opposing effects on the immunologic outcome of antigen cross-presentation depending on dendritic cell (DC) maturation status. Despite equivalent IFNAR expression, immature conventional DCs (cDCs) activate STAT1 in response to IFN-/ß, whereas exposure of mature DCs to IFN-/ß results in signaling via STAT4. Microarray analysis revealed numerous transcriptional changes resulting from the altered signaling. Importantly, STAT1 signaling resulted in significant inhibition of CD40L-induced IL-12 production, accounting for the inhibition of CD8+ T-cell activation. These data provide evidence for a molecular switch in signaling pathways concomitant with DC maturation that offers a novel mechanism by which DCs modulate the integration of signals from the surrounding environment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Frleta, C. I. Yu, E. Klechevsky, A.-L. Flamar, G. Zurawski, J. Banchereau, and A. K. Palucka Influenza Virus and Poly(I:C) Inhibit MHC Class I-Restricted Presentation of Cell-Associated Antigens Derived from Infected Dead Cells Captured by Human Dendritic Cells J. Immunol., March 1, 2009; 182(5): 2766 - 2776. [Abstract] [Full Text] [PDF] L. Cervantes-Barragan, U. Kalinke, R. Zust, M. Konig, B. Reizis, C. Lopez-Macias, V. Thiel, and B. Ludewig Type I IFN-Mediated Protection of Macrophages and Dendritic Cells Secures Control of Murine Coronavirus Infection J. Immunol., January 15, 2009; 182(2): 1099 - 1106. [Abstract] [Full Text] [PDF] Y. Hu, K.-H. Park-Min, A. Yarilina, and L. B. Ivashkiv Regulation of STAT pathways and IRF1 during human dendritic cell maturation by TNF-{alpha} and PGE2 J. Leukoc. Biol., November 1, 2008; 84(5): 1353 - 1360. [Abstract] [Full Text] [PDF] S. Sigurdsson, G. Nordmark, S. Garnier, E. Grundberg, T. Kwan, O. Nilsson, M.-L. Eloranta, I. Gunnarsson, E. Svenungsson, G. Sturfelt, et al. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5 Hum. Mol. Genet., September 15, 2008; 17(18): 2868 - 2876. [Abstract] [Full Text] [PDF] J. M. Zimmerer, G. B. Lesinski, A. S. Ruppert, M. D. Radmacher, C. Noble, K. Kendra, M. J. Walker, and W. E. Carson III Gene Expression Profiling Reveals Similarities between the In vitro and In vivo Responses of Immune Effector Cells to IFN-{alpha} Clin. Cancer Res., September 15, 2008; 14(18): 5900 - 5906. [Abstract] [Full Text] [PDF] F. Pascale, V. Contreras, M. Bonneau, A. Courbet, S. Chilmonczyk, C. Bevilacqua, M. Eparaud, V. Niborski, S. Riffault, A.-M. Balazuc, et al. Plasmacytoid Dendritic Cells Migrate in Afferent Skin Lymph J. Immunol., May 1, 2008; 180(9): 5963 - 5972. [Abstract] [Full Text] [PDF] M. Takahara, M. Miyai, M. Tomiyama, M. Mutou, A. J. Nicol, and M. Nieda Copulsing tumor antigen-pulsed dendritic cells with zoledronate efficiently enhance the expansion of tumor antigen-specific CD8+ T cells via V{gamma}9{gamma}{delta} T cell activation J. Leukoc. Biol., March 1, 2008; 83(3): 742 - 754. [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] T. Miyagi, M. P. Gil, X. Wang, J. Louten, W.-M. Chu, and C. A. Biron High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells J. Exp. Med., October 1, 2007; 204(10): 2383 - 2396. [Abstract] [Full Text] [PDF]

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