A
correction
to this article has been published: Dhodapkar et al., J. Exp. Med. 204 (10) 2489
A
correction
to this article has been published: Dhodapkar et al., J. Exp. Med. 204 (10) 2494
Published online May 14, 2007
doi:10.1084/jem.20062545
The Journal of Experimental Medicine, Vol. 204, No. 6, 1359-1369
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Dhodapkar et al.
Selective blockade of the inhibitory Fc
receptor (FcRIIB) in human dendritic cells and monocytes induces a type I interferon response program
Kavita M. Dhodapkar1,
Devi Banerjee1,
John Connolly6,
Anjli Kukreja3,
Elyana Matayeva1,
Maria Concetta Veri5,
Jeffrey V. Ravetch2,4,
Ralph M. Steinman1,4, and
Madhav V. Dhodapkar3,4
1 Lab of Cellular Physiology and Immunology, 2 Lab of Molecular Genetics and Immunology, 3 Lab of Tumor Immunology and Immunotherapy, and 4 Chris Browne Center for Immunology, The Rockefeller University, New York, NY 10021
5 MacroGenics, Inc., Rockville, MD 20850
6 Baylor Institute of Immunology Research, Dallas, TX 75204
CORRESPONDENCE Kavita M. Dhodapkar: dhodapk{at}rockefeller.edu
The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory Fc
RIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fc receptor (FcR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activator of transcription 1 (STAT1). FcR-mediated STAT1 activation is rapid and requires activating FcRs. However, this IFN response is observed without a detectable increase in the expression of type I IFNs themselves or the need to add exogenous IFNs. Induction of IFN response genes plays an important role in FcR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcRs may regulate IFN signaling in myeloid cells. Manipulation of FcR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
Abbreviations used: FcR, Fc receptor; GEP, gene expression profile; IC, immune complex; IDC, immature DC; IFI, IFN-
inducible; IFNAR, IFN- receptor; IRG, IFN response gene; STAT, signal transducer and activator of transcription.
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