IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4+ T Cells

J Immunol. 2020 Jun 1;204(11):2940-2948. doi: 10.4049/jimmunol.1901283. Epub 2020 Apr 22.


The expression of anti-inflammatory IL-10 by CD4+ T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-α blockade during T cell stimulation in CD4+ T cell/monocyte cocultures resulted in maintenance of IL-10-producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4+ T cell-only culture system. IL-10+ CD4+ T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10-CD4+ T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb-mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. However, overexpression of IKZF3 was unable to upregulate IL-10 at the mRNA or protein level in CD4+ T cells and did not drive the transcription of the IL10 promoter or putative local enhancer constructs. Collectively, these data indicate that IKZF3 is associated with but not sufficient for IL-10 expression in CD4+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Ikaros Transcription Factor / antagonists & inhibitors
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / metabolism*
  • Interleukin-10 / metabolism*
  • Lenalidomide / pharmacology
  • Lymphocyte Activation
  • RNA, Messenger / genetics*
  • Tumor Necrosis Factor-alpha / metabolism


  • CD3 Complex
  • IKZF3 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Ikaros Transcription Factor
  • Lenalidomide