Lineage-specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4

doi:10.1084/jem.190.12.1837

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© The Rockefeller University Press, 0022-1007/1999/12/1837/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 12, December 20, 1999 1837-1848

Original Article

Lineage-specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4

Sanjay Gupta^a, Man Jiang^a, Alissa Anthony^a, and Alessandra B. Pernis^a
^a Department of Medicine, Columbia University, New York, New York 10032

Correspondence to: Alessandra B. Pernis, Department of Medicine, Columbia University, 630 West 168th St., New York, NY 10032. Tel:212-305-3763 Fax:212-305-4478 E-mail:abp1{at}columbia.edu.

Interleukin (IL)-4 is an immunoregulatory cytokine that exertsdistinct biological activities on different cell types. Ourstudies indicate that interferon regulatory factor (IRF)-4 isboth a target and a modulator of the IL-4 signaling cascade.IRF-4 expression is strongly upregulated upon costimulationof B cells with CD40 and IL-4. Furthermore, we find that IRF-4can 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 repressorfactor BCL-6. Since expression of IRF-4 is mostly confined tolymphoid cells, these data provide a potential mechanism bywhich IL-4–inducible genes can be regulated in a lineage-specificmanner.

Key Words: CD40, interleukin 4, signal transducer and activator of transcription6, BCL-6, interferon regulatory factor 4

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