IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching.
IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line epsilon (GLepsilon) 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 show impaired IgE class switching, and this defect is B-cell intrinsic. The induction of GLepsilon 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 of NFIL3 in the presence of cycloheximide induces GLepsilon transcripts. Moreover, NFIL3 binds to Iepsilon promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GLepsilon transcription in response to IL-4 and subsequent IgE class switching.
Kashiwada
Masaki
M
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Levy
Deborah M
DM
McKeag
Lisa
L
Murray
Keri
K
Schröder
Andreas J
AJ
Canfield
Stephen M
SM
Traver
Geri
G
Rothman
Paul B
PB
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology*; D007134:Immunoglobulin Switch Region / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse; D015847:Interleukin-4; D007073:Immunoglobulin E