IFNγ induces monopoiesis and inhibits neutrophil development during inflammation
IFNγ induces monopoiesis and inhibits neutrophil development during inflammation
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DOI：
10.1182/blood-2011-07-367706
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发表时间：
2012-02-09
期刊：
影响因子：
20.3
通讯作者：
Nolte, Martijn A.
中科院分区：
文献类型：
--
作者：
de Bruin, Alexander M.;Libregts, Sten F.;Nolte, Martijn A.
稳态造血在感染时发生改变，但驱动这些变化的细胞和分子机制在很大程度上是未知的。造血的调节对于增加对抗入侵病原体所需的适当类型的效应细胞的输出是必不可少的。在本研究中，我们证明了促炎细胞因子IFN γ参与了炎症诱导的骨髓生成。使用小鼠模型和体外试验，我们表明，IFN γ诱导分化的单核细胞在髓系祖细胞水平的中性粒细胞。淋巴细胞性脉络丛脑膜炎病毒感染诱导野生型小鼠单细胞生成，但导致IFN γ（-/-）小鼠中性粒细胞产生增加。我们证明，IFN γ增强了髓系祖细胞中单核细胞形成诱导转录因子IRF 8和PU.1的表达，而它通过SOCS 3依赖性抑制STAT 3磷酸化降低了G-CSF驱动的中性粒细胞分化。这些结果确立了IFN γ在免疫激活过程中指导单核细胞与中性粒细胞发育的关键作用。（血。2012;119（6）：1543-1554）
Steady-state hematopoiesis is altered on infection, but the cellular and molecular mechanisms driving these changes are largely unknown. Modulation of hematopoiesis is essential to increase the output of the appropriate type of effector cell required to combat the invading pathogen. In the present study, we demonstrate that the pro-inflammatory cytokine IFN gamma is involved in orchestrating inflammation-induced myelopoiesis. Using both mouse models and in vitro assays, we show that IFN gamma induces the differentiation of monocytes over neutrophils at the level of myeloid progenitors. Infection with lymphocytic choriomeningitis virus induces monopoiesis in wild-type mice, but causes increased neutrophil production in IFN gamma(-/-) mice. We demonstrate that IFN gamma enhances the expression of the monopoiesis-inducing transcription factors IRF8 and PU.1 in myeloid progenitor cells, whereas it reduces G-CSF-driven neutrophil differentiation via a SOCS3-dependent inhibition of STAT3 phosphorylation. These results establish a critical role for IFN gamma in directing monocyte versus neutrophil development during immune activation. (Blood. 2012;119(6):1543-1554)