Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells
Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-β gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-λ. Cultures treated with IFN lambda similarly display defective lumen formation. These results demonstrate that type III IFN-λ profoundly influences the behavior of MECs and identify Blimp-1 as a critical regulator of IFN signaling cascades.
1-11
Elias, Salah
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Robertson, Elizabeth J.
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Bikoff, Elizabeth K.
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Mould, Arne W.
a913032e-73dc-419c-bbd7-b2aaba22f495
10 January 2018
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Robertson, Elizabeth J.
80d0f6ff-a50b-4fe4-a968-281d74b1e5de
Bikoff, Elizabeth K.
d58c427d-46a2-4567-9077-554ab6894da7
Mould, Arne W.
a913032e-73dc-419c-bbd7-b2aaba22f495
Elias, Salah, Robertson, Elizabeth J., Bikoff, Elizabeth K. and Mould, Arne W.
(2018)
Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells.
Scientific Reports, 8 (1), , [237].
(doi:10.1038/s41598-017-18652-9).
Abstract
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-β gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-λ. Cultures treated with IFN lambda similarly display defective lumen formation. These results demonstrate that type III IFN-λ profoundly influences the behavior of MECs and identify Blimp-1 as a critical regulator of IFN signaling cascades.
Text
s41598-017-18652-9
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Accepted/In Press date: 15 December 2017
e-pub ahead of print date: 10 January 2018
Published date: 10 January 2018
Identifiers
Local EPrints ID: 417175
URI: http://eprints.soton.ac.uk/id/eprint/417175
ISSN: 2045-2322
PURE UUID: c0a2ae92-b337-4224-990f-c21137545643
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Date deposited: 23 Jan 2018 17:30
Last modified: 16 Mar 2024 04:29
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Author:
Elizabeth J. Robertson
Author:
Elizabeth K. Bikoff
Author:
Arne W. Mould
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