KLF13 cooperates with c-Maf to regulate IL-4 expression in CD4+ T cells

J Immunol. 2014 Jun 15;192(12):5703-9. doi: 10.4049/jimmunol.1302830. Epub 2014 May 12.

Abstract

Kruppel-like factor (KLF) 13 is a transcription factor that positively regulates expression of the chemokine RANTES 3-5 d after activation of T cells. In this study, we document a key role for KLF13 in the expression of IL-4 in CD4(+) T cells. Gene expression analysis in activated T cells from Klf13(-/-) mice showed that IL-4, along with other Th2 cytokine genes, was downregulated when compared with cells from wild-type mice. The decreased levels of IL-4 were not associated with changes in expression of the Th2-inducing transcription factors GATA3 or c-Maf. Additional analysis revealed that KLF13 directly binds to IL-4 promoter regions and synergizes with c-Maf to positively regulate IL-4 expression. These results indicate that KLF13 is a positive regulator for differentiation of Th2 cells, as part of the transcriptional machinery that regulates IL-4 production in Th2 cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / immunology*
  • Proto-Oncogene Proteins c-maf / genetics
  • Proto-Oncogene Proteins c-maf / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology

Substances

  • Cell Cycle Proteins
  • Klf13 protein, mouse
  • Kruppel-Like Transcription Factors
  • Maf protein, mouse
  • Proto-Oncogene Proteins c-maf
  • Repressor Proteins
  • Interleukin-4

Associated data

  • GEO/GSE50617