Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human dendritic cells and monocytes induces a type I interferon response program
| Autor: | Jeffrey V. Ravetch, Madhav V. Dhodapkar, Anjli Kukreja, Kavita M. Dhodapkar, Ralph M. Steinman, Elyana Matayeva, Devi Banerjee, Maria Concetta Veri, John E. Connolly |
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| Rok vydání: | 2007 |
| Předmět: |
Chemokine
Immunology Blotting Western Corrections Antibodies Monocytes Article 03 medical and health sciences 0302 clinical medicine Interferon medicine Immunology and Allergy Humans STAT1 030304 developmental biology Oligonucleotide Array Sequence Analysis 0303 health sciences biology Monocyte Gene Expression Profiling Receptors IgG Correction Dendritic cell Dendritic Cells Articles Flow Cytometry 3. Good health Cell biology medicine.anatomical_structure STAT1 Transcription Factor Gene Expression Regulation Interferon Type I STAT protein biology.protein Cytokines RNA Interference Signal transduction Interferon type I 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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 FcgammaRIIB 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 Fcgamma receptor (FcgammaR)-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). FcgammaR-mediated STAT1 activation is rapid and requires activating FcgammaRs. 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 FcgammaR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcgammaR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcgammaRs may regulate IFN signaling in myeloid cells. Manipulation of FcgammaR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer. |
| Databáze: | OpenAIRE |
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