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IFN-gamma negatively regulates CpG-induced IL-10 in bone marrow-derived dendritic cells

Rafael R Flores1, Kelly A Diggs, Lauren M Tait

  • 1Department of Immunology and Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 22, 2006
PubMed

Insights

Interferon-gamma (IFN-γ) suppresses interleukin-10 (IL-10) production in dendritic cells (DCs) activated by LPS or CpG. This IFN-γ mediated inhibition enhances IL-12 production, influencing Th1/Th2 immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Dendritic cells (DCs) are crucial for regulating T-helper cell responses.
  • Interferon-gamma (IFN-γ) is a key mediator of Th1 immunity.
  • IL-10 is an anti-inflammatory cytokine often associated with Th2 responses.

Purpose of the Study:

  • To investigate the effect of IFN-γ on IL-10 and IL-12 production by DCs.
  • To elucidate the signaling pathways involved in IFN-γ-mediated regulation of these cytokines.
  • To understand the role of DCs in balancing Th1 and Th2 immune responses.

Main Methods:

  • Activation of murine dendritic cells with LPS or CpG in the presence or absence of IFN-γ.
  • Dose-response analysis of IFN-γ on cytokine production.
  • Experiments using STAT-1 knockout mice.
  • Inhibition studies using anti-IFN-β antibodies.
  • Analysis of transcriptional regulation.

Main Results:

  • LPS and CpG induced both IL-10 and IL-12 production in DCs.
  • IFN-γ dose-dependently suppressed IL-10 production while enhancing IL-12 production.
  • The inhibition of IL-10 by IFN-γ was STAT-1 dependent and transcriptionally regulated.
  • CpG-induced IL-12 production was STAT-1 dependent, but IL-10 production was not.
  • IFN-γ's inhibitory effect on IL-10 was independent of IL-12.

Conclusions:

  • Dendritic cells produce both pro-inflammatory (IL-12) and anti-inflammatory (IL-10) cytokines upon CpG stimulation.
  • IFN-γ plays a critical role in modulating DC cytokine profiles, enhancing IL-12 and suppressing IL-10.
  • This IFN-γ-mediated suppression of IL-10 by DCs represents a novel regulatory pathway impacting the balance between Th1 and Th2 immunity.

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