Milanovic Maja, Terszowski Grzegorz, Struck Daniela, Liesenfeld Oliver, Carstanjen Dirk
Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie, Berlin, Germany.
J Immunol. 2008 Oct 1;181(7):5045-53. doi: 10.4049/jimmunol.181.7.5045.
IFN consensus sequence binding protein (Icsbp) (IFN response factor-8) is a hematopoietic transcription factor with dual functions in myelopoiesis and immunity. In this study, we report a novel role of Icsbp in regulating the development of eosinophils. Loss of Icsbp in mice leads to a reduction of eosinophils in different tissues. During parasite infection with the nematode Nippostrongylus brasiliensis, Icsbp-deficient mice fail to mount eosinophilia despite a vigorous IL-5 response. Numbers of phenotypically defined eosinophil progenitors are decreased and those progenitors have, on a per-cell basis, reduced eosinophil differentiation potential. The transcription factor Gata1, crucial for eosinophil development, is reduced expressed in committed eosinophil progenitors in wells as mature eosinophils. These findings identify Icsbp as a novel transcription factor critical for the development of the eosinophil lineage.
干扰素共有序列结合蛋白(Icsbp)(干扰素反应因子8)是一种造血转录因子,在骨髓生成和免疫中具有双重功能。在本研究中,我们报道了Icsbp在调节嗜酸性粒细胞发育中的新作用。小鼠体内Icsbp的缺失导致不同组织中嗜酸性粒细胞减少。在用巴西日圆线虫进行寄生虫感染期间,尽管IL-5反应强烈,但Icsbp缺陷小鼠无法出现嗜酸性粒细胞增多。表型确定的嗜酸性粒细胞祖细胞数量减少,并且这些祖细胞在每个细胞基础上的嗜酸性粒细胞分化潜能降低。对嗜酸性粒细胞发育至关重要的转录因子Gata1在终末嗜酸性粒细胞祖细胞以及成熟嗜酸性粒细胞中表达降低。这些发现确定Icsbp是嗜酸性粒细胞谱系发育的关键新转录因子。