Case Cardiovascular Research Institute, Department of Medicine, Harrington-McLaughlin Heart and Vascular Institute, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
Immunity. 2011 May 27;34(5):715-28. doi: 10.1016/j.immuni.2011.04.014. Epub 2011 May 12.
Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1α (HIF-1α), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-κB)-dependent HIF-1α transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.
精确控制髓样细胞的激活对于最佳的宿主防御至关重要。然而，这种激活过程必须受到精细的控制，以防止失控的炎症。在此，我们发现 Kruppel 样转录因子 2（KLF2）是体内髓样细胞激活的有力调节因子。髓样细胞暴露于低氧和/或细菌产物会降低 KLF2 的表达，同时诱导缺氧诱导因子-1α（HIF-1α），这些发现在人类败血症患者中得到了重现。研究发现，髓样细胞中的 KLF2 是核因子-κB（NF-κB）依赖性 HIF-1α 转录的有效抑制剂，因此是多微生物感染和内毒素血症模型中结局的关键决定因素。综上所述，这些观察结果表明 KLF2 是体内髓样细胞激活的天然抑制剂，也是先天免疫系统的重要调节因子。
