c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells byspecifically inducing p35 gene transcription

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by anti gen presenting cells that is essential for the induction of T helper type I development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipo polysaccharide, (LPS), DNA, and CD40 ligand. To date, the regulation of IL- 12 expression at the transcriptional level has mainly been examined in macr ophages and restricted almost exclusively to the p40 gene. Here we show tha t in CDS' dendritic cells, major producers of IL-12 p70, the Rel/nuclear fa ctor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced express ion of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LP S is c-Rel dependent and regulated directly by c-Rel complexes binding to t he p35 promoter. This data establishes the IL-12 p35 gene as a new target o f c-Rel and shows that the regulation of IL-12 p70 expression at the transc riptional level by Pel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion.