THE PROTOONCOGENE C-MAF IS RESPONSIBLE FOR TISSUE-SPECIFIC EXPRESSIONOF INTERLEUKIN-4

The molecular basis for the distinctive cytokine expression of CD4+ T helper 1 (Th1) and T helper 2 (Th2) subsets remains elusive. Here, we report that the proto-oncogene c-maf, a basic region/leucine zipper tr anscription factor, controls tissue-specific expression of IL-4. c-Maf is expressed in Th2 but not Th1 clones and is induced during normal p recursor cell differentiation along a Th2 but not Th1 lineage. c-Maf b inds to a c-Maf response element (MARE) in the proximal IL-4 promoter adjacent to a site footprinted by extracts from Th2 but not Th1 clones . Ectopic expression of c-Maf transactivates the IL-4 promoter in Th1 cells, B cells, and nonlymphoid cells, a function that maps to the MAR E and Th2-specific footprint. Furthermore, c-Maf acts in synergy with the nuclear factor of activated T cells (NF-ATp) to initiate endogeneo us IL-4 production by B cells. Manipulation of c-Maf may alter Th subs et ratios in human disease.