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
doi:10.1084/jem.20062545
The Journal of Experimental Medicine, Vol. 204, No. 6, 1359-1369
The Rockefeller University Press, 0022-1007 $30.00
© Dhodapkar et al.
Selective blockade of the inhibitory Fc
receptor (Fc
RIIB) 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 (Fc
R)–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). Fc
R-mediated STAT1 activation is rapid and requires activating Fc
Rs. 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 Fc
R-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited Fc
R-mediated DC maturation. These data suggest that the balance of activating/inhibitory Fc
Rs may regulate IFN signaling in myeloid cells. Manipulation of Fc
R balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
Abbreviations used: Fc
R, 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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Gil, M., Bieniasz, M., Wierzbicki, A., Bambach, B. J., Rokita, H., Kozbor, D.
(2009). Targeting a Mimotope Vaccine to Activating Fc{gamma} Receptors Empowers Dendritic Cells to Prime Specific CD8+ T Cell Responses in Tumor-Bearing Mice. J. Immunol.
183: 6808-6818
[Abstract]
[Full Text]
-
Wenink, M. H., Santegoets, K. C. M., Roelofs, M. F., Huijbens, R., Koenen, H. J. P. M., van Beek, R., Joosten, I., Meyer-Wentrup, F., Mathsson, L., Ronnelid, J., Adema, G. J., Bonvini, E., Koenig, S., van den Berg, W. B., van Riel, P. L. C. M., Radstake, T. R. D. J.
(2009). The Inhibitory Fc{gamma}IIb Receptor Dampens TLR4-Mediated Immune Responses and Is Selectively Up-regulated on Dendritic Cells from Rheumatoid Arthritis Patients with Quiescent Disease. J. Immunol.
183: 4509-4520
[Abstract]
[Full Text]
-
Comabella, M., Lunemann, J. D., Rio, J., Sanchez, A., Lopez, C., Julia, E., Fernandez, M., Nonell, L., Camina-Tato, M., Deisenhammer, F., Caballero, E., Tortola, M. T., Prinz, M., Montalban, X., Martin, R.
(2009). A type I interferon signature in monocytes is associated with poor response to interferon-{beta} in multiple sclerosis. Brain
0: awp228v1-awp228
[Abstract]
[Full Text]
-
Johnson, T. S., Mahnke, K., Storn, V., Schonfeld, K., Ring, S., Nettelbeck, D. M., Haisma, H. J., Le Gall, F., Kontermann, R. E., Enk, A. H.
(2008). Inhibition of Melanoma Growth by Targeting of Antigen to Dendritic Cells via an Anti-DEC-205 Single-Chain Fragment Variable Molecule. Clin. Cancer Res.
14: 8169-8177
[Abstract]
[Full Text]
-
Dhodapkar, K. M., Barbuto, S., Matthews, P., Kukreja, A., Mazumder, A., Vesole, D., Jagannath, S., Dhodapkar, M. V.
(2008). Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma. Blood
112: 2878-2885
[Abstract]
[Full Text]
-
Chang, D. H., Deng, H., Matthews, P., Krasovsky, J., Ragupathi, G., Spisek, R., Mazumder, A., Vesole, D. H., Jagannath, S., Dhodapkar, M. V.
(2008). Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer. Blood
112: 1308-1316
[Abstract]
[Full Text]
-
McGaha, T. L., Karlsson, M. C. I., Ravetch, J. V.
(2008). Fc{gamma}RIIB Deficiency Leads to Autoimmunity and a Defective Response to Apoptosis in Mrl-MpJ Mice. J. Immunol.
180: 5670-5679
[Abstract]
[Full Text]