IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching

Masaki Kashiwada, Deborah M. Levy, Lisa McKeag, Keri Murray, Andreas J. Schröder, Stephen M. Canfield, Geri Traver, Paul B. Rothman

Research output: Contribution to journalArticle

Abstract

IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line ε (GLε) transcription. Previously, we and others identified a transcription factor, Nfil3, as a gene induced by IL-4 stimulation in B cells. However, the precise roles of nuclear factor, IL-3-regulated (NFIL3) in IL-4 signaling are unknown. Here, we report that NFIL3 is important for IgE class switching. NFIL3-deficient mice showimpaired IgE class switching, and this defect is B-cell intrinsic. The induction of GLε transcripts after LPS and IL-4 stimulation is significantly reduced in NFIL3-deficient B cells. Expression of NFIL3 in NFIL3-deficient B cells restores the impairment of IgE production, and overexpression ofNFIL3 in the presence of cycloheximide induces GLε transcripts. Moreover, NFIL3 binds to Iε promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GLε transcription in response to IL-4 and subsequent IgE class switching.

Original languageEnglish (US)
Pages (from-to)821-826
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Germ-line transcription
  • IL-4 signal
  • Immunoglobulin

ASJC Scopus subject areas

  • General

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