Lee Chien-kuo, Raz Regina, Gimeno Ramon, Gertner Rachel, Wistinghausen Birte, Takeshita Kenichi, DePinho Ronald A, Levy David E
Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 10016, USA.
Immunity. 2002 Jul;17(1):63-72. doi: 10.1016/s1074-7613(02)00336-9.
STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
信号转导和转录激活因子3（STAT3）已被描述为粒细胞集落刺激因子（G-CSF）驱动的细胞增殖和粒细胞生成的重要组成部分。这一观点在转基因小鼠中通过条件性基因敲除进行了验证。与预期相反，粒细胞由STAT3基因缺失的骨髓祖细胞发育而来，且STAT3基因缺失的中性粒细胞表现出成熟的效应器功能。造血祖细胞中缺乏STAT3的小鼠并未出现粒细胞生成缺陷，反而出现了中性粒细胞增多，并且骨髓细胞对G-CSF刺激反应过度。这些研究为不依赖STAT3的粒细胞生成提供了直接证据，并表明STAT3可能通过诱导信号抑制因子细胞因子信号传导抑制因子3（SOCS3）的表达来指导控制中性粒细胞数量所需的负反馈回路。
