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.[1]References
- IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Elser, B., Lohoff, M., Kock, S., Giaisi, M., Kirchhoff, S., Krammer, P.H., Li-Weber, M. Immunity (2002) [Pubmed]
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