IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils
IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils
复制标题
DOI：
10.4049/jimmunol.172.4.2059
复制
发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Huang, H
中科院分区：
文献类型：
--
作者：
Chen, LQ;Grabowski, KA;Huang, H
产生Th 2型细胞因子的先天效应细胞在Th 2细胞介导的免疫应答中至关重要。然而，尚不清楚这些细胞如何获得产生Th 2细胞因子的能力。IL-4是一种有效的诱导剂，可指导初始CD 4（+）T细胞分化为CD 4（+）Th 2效应细胞。为了确定IL-4是否可以诱导产生Th 2细胞的先天性细胞的分化和扩增，我们使用了IL-4基因被敲入的绿色荧光蛋白（gfp）基因取代的小鼠。我们发现，直接离体，IL-4以银特异性方式增加气道和肺组织中GFP（+）细胞的数量。大多数GFP（+）细胞是嗜酸性粒细胞，表明IL-4在体内扩增产生IL-4的嗜酸性粒细胞中起关键作用。与产生IL-4的CD 4 + T细胞相比，产生IL-4的嗜酸性粒细胞显示出一些独特的特征。它们在刺激时表现出IL-4基因的双等位基因表达，并且是更显性的IL-4和IL-5产生细胞。此外，我们表明，IL-4驱动骨髓祖细胞分化为Th 2型嗜酸性粒细胞在体外生产。这些结果强烈表明IL-4是一个有效的因素，指导骨髓祖细胞分化为Th 2型嗜酸性粒细胞。
Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4+ T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.