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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.
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Submitted July 22, 2004
Accepted December 24, 2004
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 Bates*
Laboratory for Immunological Research, Schering-Plough Research Institute, Dardilly, France
* Corresponding author; email: liz.bates{at}wanadoo.fr.
We previously reported the characterization of human OSCAR (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 ERK- and PI3K-dependent pathway, linked to expression of the Bcl-2 and Bcl-xL anti-apoptotic molecules. Crosslinking of hOSCAR leads to maturation of DC, as demonstrated by up-regulation of maturation markers, decrease in dextran uptake capacity, and secretion of immune effectors such as IL-8/CXCL8, IL-12 p40, MCP-1/CCL2 and MDC/CCL22. Stimulation of hOSCAR acts in conjunction with the Toll like receptor (TLR) ligands, LPS, R-848 and poly(I:C), to increase the expression of maturation markers, and to modulate cytokine release. A PI3K-dependant 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 DC 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 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.
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