Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4.
Interleukin (IL)-4 is an immunoregulatory cytokine that exerts distinct biological activities on different cell types. Our studies indicate that interferon regulatory factor (IRF)-4 is both a target and a modulator of the IL-4 signaling cascade. IRF-4 expression is strongly upregulated upon costimulation of B cells with CD40 and IL-4. Furthermore, we find that IRF-4 can interact with signal transducer and activator of transcription (Stat)6 and drive the expression of IL-4-inducible genes. The transactivating ability of IRF-4 is blocked by the repressor factor BCL-6. Since expression of IRF-4 is mostly confined to lymphoid cells, these data provide a potential mechanism by which IL-4-inducible genes can be regulated in a lineage-specific manner.
Gupta
S
S
Department of Medicine, Columbia University, New York, New York 10032, USA.
Jiang
M
M
Anthony
A
A
Pernis
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AB
D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D050835:Interferon Regulatory Factors; D015847:Interleukin-4 / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4