Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice
Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice
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DOI：
10.1073/pnas.1803936115
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发表时间：
2018-05-15
影响因子：
11.1
通讯作者：
Taniguchi, Tadatsugu
中科院分区：
文献类型：
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作者：
Yanai, Hideyuki;Chiba, Shiho;Taniguchi, Tadatsugu
干扰素调节因子3(IRF3)是许多细胞类型中细胞反应的转录调节因子，被认为是天然免疫所必需的。为了确认IRF3的S在免疫中的广泛作用，并更充分地了解它在各种细胞亚群中的作用，我们设计了IRF3-Flobled小鼠，以允许IRF3的细胞类型特异性的消融。对这些小鼠的分析证实了IRF3在体外和体内激发I型干扰素反应的一般要求。此外，当IRF3在小鼠的T细胞或B细胞中被选择性灭活时，免疫细胞个体发育和免疫细胞类型的频率没有受到影响。有趣的是，在脂多糖诱导的脓毒症休克模型中，髓系细胞中选择性的IRF3缺乏导致血清中I型干扰素水平的降低和这些小鼠的存活，表明Toll样受体4-IRF3型干扰素轴在该脓毒症模型中具有髓系特异性的致病作用。因此，IRF3标记的小鼠可以作为进一步探索该转录因子特定细胞类型功能的有用工具。
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.