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Proc Natl Acad Sci U S A. 2018 May 15;115(20):5253-5258. doi: 10.1073/pnas.1803936115. Epub 2018 Apr 30.

Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice.

Author information

1
Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan.
2
Max Planck-The University of Tokyo Center for Integrative Inflammology, 153-8505 Tokyo, Japan.
3
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
4
Japan Research and Open Innovation, 163-1488 Tokyo, Japan.
5
Animal Resource Development Unit and Genetic Engineering Team, RIKEN Center for Life Science Technologies, 650-0047 Kobe, Japan.
6
Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan; tada@m.u-tokyo.ac.jp.

Abstract

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3's broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3 Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4-IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

KEYWORDS:

Bcl2l12; IRF3; infection; inflammation; interferon

PMID:
29712834
PMCID:
PMC5960330
DOI:
10.1073/pnas.1803936115
[Indexed for MEDLINE]
Free PMC Article

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