The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4

Nat Immunol. 2007 Sep;8(9):958-66. doi: 10.1038/ni1500. Epub 2007 Aug 5.


Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17-producing T helper cells (T(H)-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4(-/-)) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into T(H)-17 cells. Transfer of wild-type T helper cells into Irf4(-/-) mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4(-/-) T helper cells had less expression of RORgammat and more expression of Foxp3, transcription factors important for the differentiation of T(H)-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4(-/-) T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also T(H)-17 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Gene Expression
  • Immunoblotting
  • Inflammation / immunology
  • Interferon Regulatory Factors / metabolism*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • interferon regulatory factor-4