Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation

Sean Diehl, Chi Wing Chow, Linda Weiss, Alois Palmetshofer, Thomas Twardzik, Laura Rounds, Edgar Serfling, Roger J. Davis, Juan Anguita, Mercedes Rincón

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Interleukin (IL)-6 is produced by professional antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells. It has been previously shown that APC-derived IL-6 promotes the differentiation of naive CD4+ T cells into effector T helper type 2 (Th2) cells. Here, we have studied the molecular mechanism for IL-6-mediated Th2 differentiation. During the activation of CD4+ T cells, IL-6 induces the production of IL-4, which promotes the differentiation of these cells into effector Th2 cells. Regulation of IL-4 gene expression by IL-6 is mediated by nuclear factor of activated T cells (NFAT), as inhibition of NFAT prevents IL-6-driven IL-4 production and Th2 differentiation. IL-6 upregulates NFAT transcriptional activity by increasing the levels of NFATc2. The ability of IL-6 to promote Th2 differentiation is impaired in CD4+ T cells that lack NFATc2, demonstrating that NFATc2 is required for regulation of IL-4 gene expression by IL-6. Regulation of NFATc2 expression and NFAT transcriptional activity represents a novel pathway by which IL-6 can modulate gene expression.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalJournal of Experimental Medicine
Volume196
Issue number1
DOIs
StatePublished - Jul 1 2002

Keywords

  • CD4 T cells
  • Cytokines
  • Gene regulation
  • IL-4
  • NFAT

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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