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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4025-4034. Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-03-007757. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-03-007757v1 108/13/4025    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 Allman, D. Articles by Chan, S. Search for Related Content PubMed PubMed Citation Articles by Allman, D. Articles by Chan, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 6, 2006 Accepted July 27, 2006 Ikaros is required for plasmacytoid dendritic cell differentiation David Allman, Marc Dalod, Carine Asselin-Paturel, Thomas Delale, Scott H Robbins, Giorgio Trinchieri, Christine A Biron, Philippe Kastner, and Susan Chan* University of Pennsylvania Centre d'Immunologie de Marseille-Luminy Schering-Plough Research Institute Brown University Institut de Genetique et de Biologie Moleculaire et Cellulaire * Corresponding author; email: scpk{at}igbmc.u-strasbg.fr. Plasmacytoid dendritic cells (pDCs) are specialized DCs that produce high levels of type I IFN upon viral infection. Despite their key immunoregulatory role, little is known about pDC ontogeny or how developmental events regulate their function. We show that mice expressing low levels of the transcription factor Ikaros (IkL/L) lack peripheral pDCs, but not other DC subsets. Loss of pDCs is associated with an inability to produce type I IFN after challenge with Toll-like receptor-7 and -9 ligands, or murine cytomegalovirus (MCMV) infection. In contrast, conventional DCs are present in normal numbers and exhibit normal responses in vivo after challenge with MCMV or inactivated toxoplasma antigen. Interestingly, IkL/L bone marrow (BM) cells contain a pDC population that appears blocked at the Ly-49Q- stage of differentiation, and fails to terminally differentiate in response to Flt-3L, a cytokine required for pDC differentiation. This differentiation block is strictly dependent on a cell-intrinsic requirement for Ikaros in pDC-committed precursors. Global gene expression profiling of IkL/L BM pDCs reveals an upregulation of genes not normally expressed, or expressed at low levels, in WT pDCs. These studies suggest that Ikaros controls pDC differentiation by silencing a large array of genes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Plasmacytoid DCs fail to soar without Ikaros Marco Colonna Blood 2006 108: 3962-3963. [Full Text] [PDF] This article has been cited by other articles: N. Zucchini, G. Bessou, S. Traub, S. H. Robbins, S. Uematsu, S. Akira, L. Alexopoulou, and M. Dalod Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection J. Immunol., May 1, 2008; 180(9): 5799 - 5803. [Abstract] [Full Text] [PDF] D. Fujiwara, B. Wei, L. L. Presley, S. Brewer, M. McPherson, M. A. Lewinski, J. Borneman, and J. Braun Systemic Control of Plasmacytoid Dendritic Cells by CD8+ T Cells and Commensal Microbiota J. Immunol., May 1, 2008; 180(9): 5843 - 5852. [Abstract] [Full Text] [PDF]

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