IFN-γ represses IL-4 expression via IRF-1 and IRF-2

被引:148
作者
Elser, B
Lohoff, M
Kock, S
Giaisi, M
Kirchhoff, S
Krammer, PH
Li-Weber, M [1 ]
机构
[1] German Canc Res Ctr, Tumorimmunol Program, D-69120 Heidelberg, Germany
[2] Univ Marburg, Inst Med Microbiol, D-35037 Marburg, Germany
关键词
D O I
10.1016/S1074-7613(02)00471-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:703 / 712
页数:10
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