Cutting edge: IL-4 production by mast cells does not require c-maf.

The c-maf transcription factor is selectively expressed in IL-4-producing Th2 cells. It has been implicated in IL-4 gene transcription based on its ability to directly activate the IL-4 gene in nonexpressing B cells and to promote IL-4-induced Th2 differentiation. However, it has not been definitively shown that IL-4 production by other cells is dependent on the presence of c-maf. Here, we show that IL-4-producing mast cells do not express the c-maf factor. Furthermore, mutation of a defined c-maf binding site within the proximal IL-4 promoter, which profoundly affects transcription in T cells, has no effect on expression of a reporter gene driven by the IL-4 promoter in mast cells. These results demonstrate that c-maf and its target binding site are not required for IL-4 production in all cell types and delineate additional cis- and trans-acting elements that contribute to the cell-type specific transcriptional regulation of IL-4.