DC-SIGN (CD209) expression is IL-4 dependent and is negatively regulated by IFN, TGF-beta, and anti-inflammatory agents.
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.
Relloso
Miguel
M
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, and Servicio de Inmuno-oncología and Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Puig-Kröger
Amaya
A
Pello
Oscar Muñiz
OM
Rodríguez-Fernández
José Luis
JL
de la Rosa
Gonzalo
G
Longo
Natividad
N
Navarro
Joaquín
J
Muñoz-Fernández
Mari Angeles
MA
Sánchez-Mateos
Paloma
P
Corbí
Angel L
AL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007372:Interferons / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D020014:K562 Cells; D037102:Lectins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D003907:Dexamethasone; D007166:Immunosuppressive Agents; D007372:Interferons; D015847:Interleukin-4; D037102:Lectins; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin