Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression

Jyothi Rengarajan, Kerri A. Mowen, Kathryn D. McBride, Erica D. Smith, Harinder Singh, Laurie H. Glimcher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system-restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4-inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalJournal of Experimental Medicine
Volume195
Issue number8
DOIs
StatePublished - Apr 15 2002

Keywords

  • IL-4
  • IRF4
  • Interaction
  • NFAT
  • Transcriptional regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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