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

Fingerprint

Immunoglobulin Class Switching
Interleukin-3
Interleukin-4
Immunoglobulin E
Transcription Factors
Germ Cells
B-Lymphocytes
Cycloheximide

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. / Kashiwada, Masaki; Levy, Deborah M.; McKeag, Lisa; Murray, Keri; Schröder, Andreas J.; Canfield, Stephen M.; Traver, Geri; Rothman, Paul B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 2, 2010, p. 821-826.

Research output: Contribution to journalArticle

Kashiwada, Masaki ; Levy, Deborah M. ; McKeag, Lisa ; Murray, Keri ; Schröder, Andreas J. ; Canfield, Stephen M. ; Traver, Geri ; Rothman, Paul B. / IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 2. pp. 821-826.
@article{c3326e81730e4f39ab76561467150248,
title = "IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching",
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.",
keywords = "Germ-line transcription, IL-4 signal, Immunoglobulin",
author = "Masaki Kashiwada and Levy, {Deborah M.} and Lisa McKeag and Keri Murray and Schr{\"o}der, {Andreas J.} and Canfield, {Stephen M.} and Geri Traver and Rothman, {Paul B}",
year = "2010",
doi = "10.1073/pnas.0909235107",
language = "English (US)",
volume = "107",
pages = "821--826",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2",

}

TY - JOUR

T1 - IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching

AU - Kashiwada, Masaki

AU - Levy, Deborah M.

AU - McKeag, Lisa

AU - Murray, Keri

AU - Schröder, Andreas J.

AU - Canfield, Stephen M.

AU - Traver, Geri

AU - Rothman, Paul B

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Germ-line transcription

KW - IL-4 signal

KW - Immunoglobulin

UR - http://www.scopus.com/inward/record.url?scp=76249112770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76249112770&partnerID=8YFLogxK

U2 - 10.1073/pnas.0909235107

DO - 10.1073/pnas.0909235107

M3 - Article

C2 - 20080759

AN - SCOPUS:76249112770

VL - 107

SP - 821

EP - 826

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2

ER -