NFIL3/E4BP4 controls type 2 T helper cell cytokine expression

EMBO J. 2011 May 18;30(10):2071-82. doi: 10.1038/emboj.2011.111. Epub 2011 Apr 15.


Type 2 T helper (T(H)2) cells are critical for the development of allergic immune responses; however, the molecular mechanism controlling their effector function is still largely unclear. Here, we report that the transcription factor NFIL3/E4BP4 regulates cytokine production and effector function by T(H)2 cells. NFIL3 is highly expressed in T(H)2 cells but much less in T(H)1 cells. Production of interleukin (IL)-13 and IL-5 is significantly increased in Nfil3(-/-) T(H)2 cells and is decreased by expression of NFIL3 in wild-type T(H)2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL-4 production is decreased in Nfil3(-/-) T(H)2 cells. Increased IL-13 and IL-5 together with decreased IL-4 production by antigen-stimulated splenocytes from the immunized Nfil3(-/-) mice was also observed. The ability of NFIL3 to alter T(H)2 cytokine production is a T-cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T(H)2 responses.

Publication types

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

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Gene Expression Regulation*
  • Interleukin-13 / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Interleukin-5 / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Transcription, Genetic


  • Basic-Leucine Zipper Transcription Factors
  • Interleukin-13
  • Interleukin-5
  • Nfil3 protein, mouse
  • Interleukin-4