Abstract
Interleukin 22 (IL-22), which is produced by cells of the TH17 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 TH17 cells, transforming growth factor-β (TGF-β) 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-β 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-β, 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-β-dependent suppression of IL-22 production in TH17 cells.
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S.R. did most of the experiments and analyzed the data; R.N. contributed to Figures 2, 4 and 5 and Supplementary Figure 4; C.E. contributed to Figures 2 and 5 and Supplementary Figure 1; W.Z. and H.S. contributed to Figure 7; Y.Z. contributed to Figures 1 and 2; N.O. and J.D. cloned c-Maf and RORγt constructs; J.H. analyzed Affymetrix data; W.O. devised and planned the project; and S.R. and W.O. wrote the manuscript.
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Rutz, S., Noubade, R., Eidenschenk, C. et al. Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells. Nat Immunol 12, 1238–1245 (2011). https://doi.org/10.1038/ni.2134
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DOI: https://doi.org/10.1038/ni.2134
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