Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells
Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells
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DOI：
10.1182/blood-2010-06-291898
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发表时间：
2011-02-17
期刊：
影响因子：
20.3
通讯作者：
Okumura, Ko
中科院分区：
文献类型：
--
作者：
Kanada, Shunsuke;Nishiyama, Chiharu;Okumura, Ko
在这项研究中，我们研究了转录因子PU.1在调节树突状细胞(DC)CD80和CD86表达中的作用。染色质免疫沉淀实验表明，PU.1与骨髓来源的DC中的CD80和CD86启动子有结构性结合。此外，在报告实验中，共表达PU.1导致CD80和CD86启动子的反式激活。电迁移率凝胶位移实验证实PU.1与顺式增强区结合。正如预期的那样，短干扰RNA(SiRNA)抑制骨髓来源的DC中PU.1的表达，导致CD80和CD86表达显著下调。此外，在缺乏单核细胞/DC相关生长因子和/或细胞因子的情况下，PU.1在小鼠骨髓来源的谱系阴性细胞中过表达可诱导CD80和CD86的表达。根据这些结果，我们认为PU1是CD80和CD86表达的关键因子。我们还发现，皮下注射PU.1 siRNA或局部应用乳化液PU.1 siRNA有效地抑制了小鼠的接触性超敏反应。我们的结果表明PU1是治疗免疫相关疾病的潜在靶点。(血。2011；117(7)：2211-2222)
In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cyto- kines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases. (Blood. 2011;117(7):2211-2222)