Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in T(H)17 cells

Nat Immunol. 2011 Oct 16;12(12):1238-45. doi: 10.1038/ni.2134.

Abstract

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-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 T(H)17 cells.

MeSH terms

  • Animals
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Binding Sites / genetics
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Interleukins / biosynthesis*
  • Interleukins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Nucleotide Motifs
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-maf / genetics
  • Proto-Oncogene Proteins c-maf / metabolism*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Transcription, Genetic
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Proto-Oncogene Proteins c-maf
  • Receptors, Aryl Hydrocarbon
  • Transforming Growth Factor beta
  • interleukin-22