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The Journal of Immunology, 2002, 168: 2634-2643.
Copyright © 2002 by The American Association of Immunologists

DC-SIGN (CD209) Expression Is IL-4 Dependent and Is Negatively Regulated by IFN, TGF-{beta}, and Anti-Inflammatory Agents1

Miguel Relloso2,*, Amaya Puig-Kröger*, Oscar Muñiz Pello*, José Luis Rodríguez-Fernández{dagger}, Gonzalo de la Rosa{dagger}, Natividad Longo{dagger}, Joaquín Navarro{ddagger}, Mari Angeles Muñoz-Fernández{ddagger}, Paloma Sánchez-Mateos{dagger} and Angel L. Corbí3,*

* Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, and {dagger} Servicio de Inmuno-oncología and {ddagger} Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain

Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) is a monocyte-derived dendritic cell (MDDC)-specific lectin which participates in dendritic cell (DC) migration and DC-T lymphocyte interactions at the initiation of immune responses and enhances trans-infection of T cells through its HIV gp120-binding ability. The generation of a DC-SIGN-specific mAb has allowed us to determine that the acquisition of DC-SIGN expression during the monocyte-DC differentiation pathway is primarily induced by IL-4, and that GM-CSF cooperates with IL-4 to generate a high level of DC-SIGN mRNA and cell surface expression on immature MDDC. IL-4 was capable of inducing DC-SIGN expression on monocytes without affecting the expression of other MDDC differentiation markers. By contrast, IFN-{alpha}, IFN-{gamma}, and TGF-{beta} were identified as negative regulators of DC-SIGN expression, as they prevented the IL-4-dependent induction of DC-SIGN mRNA on monocytes, and a similar inhibitory effect was exerted by dexamethasone, an inhibitor of the monocyte-MDDC differentiation pathway. The relevance of the inhibitory action of dexamethasone, IFN, and TGF-{beta} on DC-SIGN expression was emphasized by their ability to inhibit the DC-SIGN-dependent HIV-1 binding to differentiating MDDC. These results demonstrate that DC-SIGN, considered as a MDDC differentiation marker, is a molecule specifically expressed on IL-4-treated monocytes, and whose expression is subjected to a tight regulation by numerous cytokines and growth factors. This feature might help in the development of strategies to modulate the DC-SIGN-dependent cell surface attachment of HIV for therapeutic purposes.




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