IFN-gamma represses IL-4 expression via IRF-1 and IRF-2.
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.
Elser
Bernd
B
Tumorimmunology Program, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Lohoff
Michael
M
Kock
Sonja
S
Giaisi
Marco
M
Kirchhoff
Sabine
S
Krammer
Peter H
PH
Li-Weber
Min
M
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D019169:Jurkat Cells; D010750:Phosphoproteins / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma