IFN-gamma Represses IL-4 Expression via IRF-1 and IRF-2

Immunity. 2002 Dec;17(6):703-12. doi: 10.1016/s1074-7613(02)00471-5.

Abstract

Polarization of CD4(+) T helper cells toward either a Th1 or Th2 response can significantly influence host immunity to pathogens. IL-4 and IFN-gamma are the signature cytokines of Th2 and Th1 cells, respectively. IFN-gamma was shown to assist Th1 development by promoting IL-12 and IL-12 receptor expression. So far, direct influence of Th2 cytokine expression by IFN-gamma has not been described. We show here that IFN-gamma directly suppresses IL-4 gene expression. IRF-1 and IRF-2 induced by IFN-gamma bind to three distinct IL-4 promoter sites and function as transcriptional repressors. Our data demonstrate a direct negative feedback of IFN-gamma on expression of the Th2 cytokine gene IL-4 and, thus, provide evidence for another important mechanism by which IFNgamma assists Th1 and attenuates Th2 responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Interferon-gamma / pharmacology*
  • Interleukin-4 / genetics*
  • Interleukin-4 / immunology
  • Jurkat Cells
  • Phosphoproteins / genetics*
  • Phosphoproteins / immunology
  • Repressor Proteins*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • IRF1 protein, human
  • IRF2 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Phosphoproteins
  • Repressor Proteins
  • Transcription Factors
  • Interleukin-4
  • Interferon-gamma