Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.
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DOI：
10.1371/journal.pone.0152385
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Dunnwald M
中科院分区：
文献类型：
--
作者：
Joly S;Rhea L;Volk P;Moreland JG;Dunnwald M
干扰素调节因子6（Interferon Regulatory Factor，IRF）是IRF家族的成员之一，对表皮和口面部胚胎发育至关重要。Irf 6在角质形成细胞中强烈表达，在角质形成细胞中它调节表皮增殖、分化和迁移。Irf 6在Toll样受体2依赖性趋化因子基因表达中的最近作用也在上皮细胞系中报道。然而，Irf 6在先天免疫细胞中的功能以前没有报道。在本研究中，我们研究了Irf 6在骨髓来源的中性粒细胞和巨噬细胞中的表达和功能。我们在这里显示，使用lysosymeM表达细胞中Irf 6的条件性敲除，Irf 6是抵抗LPS诱导的内毒素休克所必需的。此外，与野生型细胞相比，Irf 6缺陷型骨髓来源的中性粒细胞在体外表现出增加的趋化指数和速度。TLR 4-特异性KC和IL 6分泌上调在Irf 6缺陷骨髓来源的巨噬细胞在体外。这些细胞还表现出磷酸化IkBa水平的增加。总的来说，我们的研究结果表明Irf 6在抵抗内毒素休克中的作用，这是由于NF κ B介导的细胞因子产生的改变。
Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.