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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 Guptaa, Man Jianga, Alissa Anthonya, and Alessandra B. Pernisa

a Department of Medicine, Columbia University, New York, New York 10032
Department of Medicine, Columbia University, 630 West 168th St., New York, NY 10032.212-305-4478212-305-3763

abp1{at}columbia.edu

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.

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

Abbreviations used in this paper: BCL-6, B cell lymphomas 6; EMSA, electrophoretic mobility shift assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GAS, IFN-{gamma}–activated site(s); GBP, guanylate binding protein; GSH, glutathione; GST, GSH S-transferase; ICSBP, IFN consensus sequence binding protein; IRF, IFN regulatory factor; ISGF, IFN-stimulated gene factor; ISRE, IFN-stimulated regulatory element; NF-{kappa}B, nuclear factor {kappa}B; STAT, signal transducer and activator of transcription; WCE, whole cell extract; wt, wild-type.

© 1999 The Rockefeller University Press


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