Interferon-γ switches monocyte differentiation from dendritic cells to macrophages
Interferon-γ switches monocyte differentiation from dendritic cells to macrophages
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DOI：
10.1182/blood-2002-04-1164
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发表时间：
2003-01-01
期刊：
影响因子：
20.3
通讯作者：
Jeannin, P
中科院分区：
文献类型：
--
作者：
Delneste, Y;Charbonnier, P;Jeannin, P
人单核细胞根据环境信号的性质分化为树突状细胞（DC）或巨噬细胞。用粒细胞-巨噬细胞集落刺激因子（GM-CSF）加白细胞介素4（IL-4）刺激单核细胞产生DC。我们在这里测试是否干扰素-γ（IFN-γ），一种有效的巨噬细胞激活剂，可以调节单核细胞分化。向IL-4加GM-CSF刺激的单核细胞中加入IFN-γ可将其从DC分化为CD 14（-）CD 64（+）巨噬细胞。IFN-γ通过在转录水平上起作用而增加IL-4加GM-CSF刺激的单核细胞的巨噬细胞集落刺激因子（M-CSF）和IL-6的产生，并且与IL-4一起起作用以上调M-CSF但不上调IL-6的产生。IFN-γ还增加M-CSF受体内化。来自中和实验的结果表明，M-CSF和IL-6都参与IFN-γ使单核细胞从DC分化为巨噬细胞的能力。最后，IFN-γ的这种作用仅限于分化的早期阶段。当添加到未成熟的DC中时，IFN-γ上调IL-6但不上调M-CSF的产生，并且即使在外源性M-CSIF存在下也不将它们转化为巨噬细胞。总之，IFN-γ通过自分泌M-CSF和IL-6的产生将单核细胞分化为巨噬细胞而不是DC。这些数据表明，IFN-γ控制抗原呈递细胞的分化，从而揭示了IFN-γ协调特异性免疫应答结果的新机制。(C)2003年，美国血液学会。
Human monocytes differentiate into dendritic cells (DCs) or macrophages according to the nature of environmental signals. Monocytes stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL-4) yield DCs. We tested here whether interferon-gamma (IFN-gamma), a potent activator of macrophages, may modulate monocyte differentiation. Addition of IFN-gamma to IL-4 plus GM-CSF-stimulated monocytes switches their differentiation from DCs to CD14(-)CD64(+) macrophages. IFN-gamma increases macrophage colony-stimulating factor (M-CSF) and IL-6 production by IL-4 plus GM-CSF-stimulated monocytes by acting at the transcriptional level and acts together with IL-4 to up-regulate M-CSF but not IL-6 production. IFN-gamma also increases M-CSF receptor internalization. Results from neutralizing experiments show that both M-CSF and IL-6 are involved in the ability of IFN-gamma to skew monocyte differentiation from DCs to macrophages. Finally, this effect of IFN-gamma is limited to early stages of differentiation. When added to immature DCs, IFN-gamma upregulates IL-6 but not M-CSF production and does not convert them to macrophages, even in the presence of exogenous M-CSIF. In conclusion, IFN-gamma shifts monocyte differentiation to macrophages rather than DCs through autocrine M-CSF and IL-6 production. These data show that IFN-gamma controls the differentiation of antigen-presenting cells and thereby reveals a new mechanism by which IFN-gamma orchestrates the outcome of specific immune responses. (C) 2003 by The American Society of Hematology.