Aiolos promotes TH17 differentiation by directly silencing Il2 expression

Nat Immunol. 2012 Jul 1;13(8):770-7. doi: 10.1038/ni.2363.


CD4(+) interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are instrumental in the immune response to pathogens. However, an overactive T(H)17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of T(H)17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during T(H)7 differentiation is not understood. Here we report that under T(H)17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting T(H)17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of T(H)17 cells that actively limits IL-2 production and promotes their differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Colitis / immunology
  • Gene Expression Regulation
  • Ikaros Transcription Factor
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Aryl Hydrocarbon / metabolism
  • STAT3 Transcription Factor / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Ahr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Ikzf3 protein, mouse
  • Interleukin-2
  • Receptors, Aryl Hydrocarbon
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Ikaros Transcription Factor
  • Interferon-gamma