Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice.
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.
['Yanai|Hideyuki|H|', 'Chiba|Shiho|S|', 'Hangai|Sho|S|', 'Kometani|Kohei|K|', 'Inoue|Asuka|A|', 'Kimura|Yoshitaka|Y|', 'Abe|Takaya|T|', 'Kiyonari|Hiroshi|H|', 'Nishio|Junko|J|', 'Taguchi-Atarashi|Naoko|N|', 'Mizushima|Yu|Y|', 'Negishi|Hideo|H|', 'Grosschedl|Rudolf|R|', 'Taniguchi|Tadatsugu|T|']
D000818:Animals D005786:Gene Expression Regulation D007113:Immunity, Innate D007249:Inflammation D050838:Interferon Regulatory Factor-3 D008070:Lipopolysaccharides D051379:Mice D018345:Mice, Knockout D022423:Myeloid Cells D015398:Signal Transduction D013601:T-Lymphocytes
IRF3 inflammation Bcl2l12 infection interferon