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

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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Figure 1: TGF-β suppresses IL-22 production in TH17 cells.
Figure 2: Inhibition of IL-22 by TGF-β is independent of IL-9, IL-10 and IL-21 but correlates with the induction of c-Maf.
Figure 3: Inhibition of IL-22 production in T cells by c-Maf alone.
Figure 4: TGF-β-mediated suppression of IL-22 requires c-Maf.
Figure 5: TGF-β and c-Maf do not repress the expression of RORγt or BATF.
Figure 6: High expression of IL-22 does not require AhR.
Figure 7: Binding of c-Maf to a motif in the proximal Il22 promoter.
Figure 8: Repressor activity of c-Maf in the regulation of IL-22.

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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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Correspondence to Wenjun Ouyang.

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All authors are employees of Genentech.

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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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