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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3623-3632. Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-07-2809. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2809v1 105/9/3623    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 Merck, E. Articles by Bates, E. E. M. Search for Related Content PubMed PubMed Citation Articles by Merck, E. Articles by Bates, E. E. M. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Fc receptor -chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses Estelle Merck, Blandine de Saint-Vis, Mathieu Scuiller, Claude Gaillard, Christophe Caux, Giorgio Trinchieri, and Elizabeth E. M. Bates From the Schering-Plough Research Institute, Laboratory for Immunological Research, Dardilly, France. We previously reported the characterization of human osteoclast-associated receptor (hOSCAR), a novel Fc receptor -chain (FcR)–associated receptor expressed by myeloid cells. Here we show that ligation of hOSCAR by specific antibodies promotes dendritic cell (DC) survival by an extracellular signal-regulated kinase (ERK)- and phosphatidylinositol 3-kinase (PI3K)–dependent pathway, linked to expression of the Bcl-2 and Bcl-xL antiapoptotic molecules. Crosslinking of hOSCAR leads to maturation of DCs, as demonstrated by up-regulation of maturation markers, decrease in dextran uptake capacity, and secretion of immunesystem effectors such as interleukin-8 (IL-8)/CXC chemokine ligand 8 (CXCL8), IL-12 p40, monocyte chemoattractant protein-1 (MCP-1)/chemokine receptor ligand 2 (CCL2) and macrophage-derived chemokine (MDC)/CCL22. Stimulation of hOSCAR acts in conjunction with the Toll-like receptor (TLR) ligands, lipopolysaccharide (LPS), R-848, and polyinosinic-polycytidylic acid (poly(I:C)), to increase the expression of maturation markers, and to modulate cytokine release. A PI3K-dependent up-regulation of IL-10 release is observed with all the TLR ligands used, whereas regulation of IL-12 production is variable depending on the TLR stimulated. hOSCAR engagement on DCs did not significantly increase the proliferation of naive T cells; however, when co-incubated with TLR ligands, an enhanced proliferation was observed. The percentage of interferon (IFN)––producing T cells is decreased when hOSCAR engagement is combined with LPS stimulation. Altogether, these data suggest that hOSCAR may modulate the responses of both innate resistance and adaptive immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. T. Young, E. C. P. Waller, R. Patel, A. Roghanian, J. M. Austyn, and J. Trowsdale The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells Blood, March 15, 2008; 111(6): 3090 - 3096. [Abstract] [Full Text] [PDF] I. Dunn-Siegrist, O. Leger, B. Daubeuf, Y. Poitevin, F. Depis, S. Herren, M. Kosco-Vilbois, Y. Dean, J. Pugin, and G. Elson Pivotal Involvement of Fc{gamma} Receptor IIA in the Neutralization of Lipopolysaccharide Signaling via a Potent Novel Anti-TLR4 Monoclonal Antibody 15C1 J. Biol. Chem., November 30, 2007; 282(48): 34817 - 34827. [Abstract] [Full Text] [PDF] R. Fudala, A. Krupa, M. A. Matthay, T. C. Allen, and A. K. Kurdowska Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of neutrophils Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L364 - L374. [Abstract] [Full Text] [PDF] E. Merck, C. Gaillard, M. Scuiller, P. Scapini, M. A. Cassatella, G. Trinchieri, and E. E. M. Bates Ligation of the FcR{gamma} Chain-Associated Human Osteoclast-Associated Receptor Enhances the Proinflammatory Responses of Human Monocytes and Neutrophils. J. Immunol., March 1, 2006; 176(5): 3149 - 3156. [Abstract] [Full Text] [PDF]

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