Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells

Immunity. 2010 Aug 27;33(2):192-202. doi: 10.1016/j.immuni.2010.07.014. Epub 2010 Jul 30.


Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper 2 (Th2) and Th17 cells. Herein, we report that IRF4 is also crucial for the development and function of an interleukin-9 (IL-9)-producing CD4(+) T cell subset designated Th9. IRF4-deficient CD4(+) T cells failed to develop into IL-9-producing Th9 cells, and IRF4-specific siRNA inhibited IL-9 production in wild-type CD4(+) T cells. Chromatin-immunoprecipitation (ChIP) analyses revealed direct IRF4 binding to the Il9 promoter in Th9 cells. In a Th9-dependent asthma model, neutralization of IL-9 substantially ameliorated asthma symptoms. The relevance of these findings is emphasized by the fact that the induction of IL-9 production also occurs in human CD4(+) T cells accompanied by the upregulation of IRF4. Our data clearly demonstrate the central function of IRF4 in the development of Th9 cells and underline the contribution of this T helper cell subset to the pathogenesis of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / genetics
  • Asthma / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Humans
  • Interferon Regulatory Factors / deficiency
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Interferon Regulatory Factors / metabolism
  • Interleukin-9 / biosynthesis
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering / genetics
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Interferon Regulatory Factors
  • Interleukin-9
  • RNA, Small Interfering
  • interferon regulatory factor-4