4.7 Article

Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells

Journal

SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-18652-9

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Funding

  1. Wellcome Trust [090532/Z/09/Z, 102811, 08957]

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The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-beta 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-lambda. Cultures treated with IFN lambda similarly display defective lumen formation. These results demonstrate that type III IFN-lambda profoundly influences the behavior of MECs and identify Blimp-1 as a critical regulator of IFN signaling cascades.

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