NDLI: Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

Content Provider	PubMed Central
Author	Dhodapkar, Kavita M. Banerjee, Devi Connolly, John Kukreja, Anjli Matayeva, Elyana Veri, Maria Concetta Ravetch, Jeffrey V. Steinman, Ralph M. Dhodapkar, Madhav V.
Abstract	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 FcγRIIB 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 Fcγ receptor (FcγR)–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). FcγR-mediated STAT1 activation is rapid and requires activating FcγRs. 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 FcγR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcγR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcγRs may regulate IFN signaling in myeloid cells. Manipulation of FcγR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
Related Links	http://dx.doi.org/10.1084/jem.20062545
Ending Page	1369
Page Count	11
Starting Page	1359
File Format	PDF
ISSN	00221007
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	6
Volume Number	204
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2007-06-11
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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