The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells

Nat Immunol. 2011 May;12(5):450-9. doi: 10.1038/ni.2020. Epub 2011 Apr 3.


The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (T(H)2) cells but also by T(H)1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic T(H)1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3(-/-); called 'E4bp4(-/-)' here) T(H)1 cells, regulatory T cells (T(reg) cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional T(H)1 cells. E4bp4(-/-) T(H)2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in T(H)1 cells and IL-10 in T(H)1 cells, T(H)2 cells, T(reg) cells and NKT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Electrophoretic Mobility Shift Assay
  • Flow Cytometry
  • Interleukin-10 / immunology*
  • Interleukin-13 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Specific Pathogen-Free Organisms
  • Transcription, Genetic


  • Basic-Leucine Zipper Transcription Factors
  • Interleukin-13
  • Nfil3 protein, mouse
  • Interleukin-10