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Class II transactivator and class II MHC gene expression in microglia: modulation by the cytokines TGF-beta, IL-4,

G M O'Keefe1, V T Nguyen, E N Benveniste

  • 1Department of Cell Biology, University of Alabama at Birmingham, 35294-0005, USA.

European Journal of Immunology
|May 6, 1999
PubMed

Insights

Cytokines TGF-beta1, IL-4, and IL-10 can inhibit interferon-gamma (IFN-γ)-induced class II MHC and CIITA gene expression in microglia. These cytokines affect CIITA mRNA transcription, impacting immune responses.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Immunology

Background:

  • Microglia, the brain's resident macrophages, play key roles in immune responses through functions like cytokine production and antigen presentation.
  • Class II Major Histocompatibility Complex (MHC) molecules are crucial for T cell activation, presenting antigenic peptides to helper T cells.
  • The expression of Class II MHC genes is tightly regulated by the class II transactivator (CIITA) transcription factor.

Purpose of the Study:

  • To investigate the impact of immunomodulatory cytokines on interferon-gamma (IFN-γ)-induced Class II MHC and CIITA gene expression in microglia.
  • To compare the effects of cytokines on both primary microglia and a murine microglial cell line (EOC 20).

Main Methods:

  • Flow cytometry was used to analyze surface expression of Class II MHC molecules.
  • Ribonuclease protection assay was employed to assess messenger RNA (mRNA) levels of CIITA and Class II MHC.
  • Experiments were conducted on both primary murine microglia and the EOC 20 microglial cell line.

Main Results:

  • Interferon-gamma (IFN-γ) induces Class II MHC and CIITA expression in microglia.
  • Cytokines TGF-β1, IL-4, and IL-10 inhibited IFN-γ-induced Class II MHC and CIITA expression in the EOC 20 cell line.
  • These inhibitory effects were mediated by reduced CIITA and Class II MHC mRNA levels, likely at the transcriptional level.
  • While IL-10 and TGF-β1 inhibited expression in primary microglia, IL-4 showed an enhancing effect, indicating cell-type specific responses.

Conclusions:

  • Immunomodulatory cytokines differentially regulate IFN-γ-induced Class II MHC and CIITA expression in microglia.
  • TGF-β1, IL-4, and IL-10 primarily act by inhibiting CIITA gene transcription.
  • Differences in IL-4 responsiveness highlight the complexity of microglial responses and suggest coordinated modulation of CIITA and Class II MHC gene expression.

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