Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells

Interleukin 22 (IL-22), which is produced by cells of the T(H)17 subset of helper T cells and other leukocytes, not only enhances proinflammatory innate defense mechanisms in epithelial cells but also provides crucial protection to tissues from damage caused by inflammation and infection. In T(H)17 cells, transforming growth factor-beta (TGF-beta) regulates IL-22 and IL-17 differently. IL-6 alone induces T cells to produce only IL-22, whereas the combination of IL-6 and high concentrations of TGF-beta results in the production of IL-17 but not IL-22 by T cells. Here we identify the transcription factor c-Maf, which is induced by TGF-beta, as a downstream repressor of Il22. We found that c-Maf bound to the Il22 promoter and was both necessary and sufficient for the TGF-beta-dependent suppression of IL-22 production in T(H)17 cells.