Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression

Eur J Immunol. 2010 Nov;40(11):3198-209. doi: 10.1002/eji.201040570. Epub 2010 Oct 27.


The transcription factor interferon regulatory factor 4 (IRF4) was originally found to be preferentially expressed in lymphoid cells and to be required for the function, differentiation, and homeostasis of both mature T and B lymphocytes. Recent studies have indicated that IRF4 is also involved in early B-cell development. However, the role of IRF4 in intrathymic T-cell development remains unknown. In this study, we show that IRF4 is upregulated in TCR-signaled thymocytes and is predominantly expressed in CD4 single-positive (SP), but not in CD8 SP, cells. T-cell-specific overexpression of IRF4 impaired the generation and maturation of CD8 SP thymocytes. Further analysis revealed that IRF4 selectively bound to the distal promoter region of Runx3 and repressed its transcription, probably through the deacetylation of histones H3 and H4 in intermediate CD4(+) CD8(low) cells and CD4 SP thymocytes. Similar to the effect of Runx3 deficiency, transgenic expression of IRF4 led not only to an aberrantly high expression of CD4 surface molecules on intermediate CD4(+) CD8(low) cells and CD8 SP thymocytes, but also impaired CD8(+) T-cell function. Taken together, our data suggest that IRF4 plays an important role in the regulation of Runx3 expression and CD4(+) /CD8(+) thymocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / immunology*
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Histones / genetics
  • Histones / immunology
  • Histones / metabolism
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Interferon Regulatory Factors / metabolism
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology


  • CD4 Antigens
  • Core Binding Factor Alpha 3 Subunit
  • Histones
  • Interferon Regulatory Factors
  • Runx3 protein, mouse
  • interferon regulatory factor-4