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DC-SIGN (CD209) expression is IL-4 dependent and is negatively regulated by IFN, TGF-beta, and anti-inflammatory

Miguel Relloso1, Amaya Puig-Kröger, Oscar Muñiz Pello

  • 1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, and Servicio de Inmuno-oncología and Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Journal of Immunology (Baltimore, Md. : 1950)
|March 9, 2002
PubMed

Insights

Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) expression on monocytes is induced by IL-4 and regulated by cytokines. This finding is crucial for developing strategies to control HIV attachment to cells.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) is a lectin on monocyte-derived dendritic cells (MDDCs).
  • DC-SIGN plays roles in dendritic cell (DC) migration, DC-T cell interactions, and HIV trans-infection.
  • Understanding DC-SIGN regulation is key for immune response modulation and HIV therapeutics.

Purpose of the Study:

  • To investigate the regulatory mechanisms of DC-SIGN expression during monocyte-to-MDDC differentiation.
  • To identify cytokines and factors that induce or inhibit DC-SIGN expression.
  • To explore the therapeutic potential of modulating DC-SIGN expression for HIV control.

Main Methods:

  • Generation of a DC-SIGN-specific monoclonal antibody (mAb).
  • Treatment of monocytes with various cytokines (IL-4, GM-CSF, IFN-alpha, IFN-gamma, TGF-beta) and dexamethasone.
  • Analysis of DC-SIGN mRNA and cell surface expression.
  • Assessment of HIV-1 binding to differentiating MDDCs.

Main Results:

  • IL-4 is the primary inducer of DC-SIGN expression on monocytes.
  • GM-CSF cooperates with IL-4 to enhance DC-SIGN mRNA and surface expression on immature MDDCs.
  • IFN-alpha, IFN-gamma, TGF-beta, and dexamethasone inhibit IL-4-induced DC-SIGN expression.
  • Inhibitory factors reduce DC-SIGN-dependent HIV-1 binding to differentiating MDDCs.

Conclusions:

  • DC-SIGN is an IL-4-induced marker of monocyte differentiation into MDDCs.
  • DC-SIGN expression is tightly regulated by multiple cytokines and growth factors.
  • Modulating DC-SIGN expression offers a potential therapeutic strategy against HIV infection.

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