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
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U2 - 10.1073/pnas.0909235107
DO - 10.1073/pnas.0909235107
M3 - Article
C2 - 20080759
AN - SCOPUS:76249112770
SN - 0027-8424
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
IS - 2
ER -