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

Hideyuki Yanai, Shiho Chiba, Sho Hangai, Kohei Kometani, Asuka Inoue, Yoshitaka Kimura, Takaya Abe, Hiroshi Kiyonari, Junko Nishio, Naoko Taguchi-Atarashi, Yu Mizushima, Hideo Negishi, Rudolf Grosschedl, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5253-5258
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number20
DOIs
Publication statusPublished - 2018 May 15
Externally publishedYes

Keywords

  • Bcl2l12
  • IRF3
  • Infection
  • Inflammation
  • Interferon

ASJC Scopus subject areas

  • General

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  • Cite this

    Yanai, H., Chiba, S., Hangai, S., Kometani, K., Inoue, A., Kimura, Y., Abe, T., Kiyonari, H., Nishio, J., Taguchi-Atarashi, N., Mizushima, Y., Negishi, H., Grosschedl, R., & Taniguchi, T. (2018). Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice. Proceedings of the National Academy of Sciences of the United States of America, 115(20), 5253-5258. https://doi.org/10.1073/pnas.1803936115