Cutting Edge: An Inactive Chromatin Configuration at the IL-10 Locus in Human Neutrophils
Cutting Edge: An Inactive Chromatin Configuration at the IL-10 Locus in Human Neutrophils
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DOI：
10.4049/jimmunol.1203022
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Cassatella, Marco A.
中科院分区：
文献类型：
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作者：
Tamassia, Nicola;Zimmermann, Maili;Cassatella, Marco A.
为了确定白细胞介素-10在人吞噬细胞中表达的分子基础，我们评估了白细胞介素-10基因组位点的染色质修饰状态。我们分析了与活化、抑制或准备转录激活的基因相关的组蛋白的翻译后修饰，包括H3K4me3、H4Ac、H3K27Ac和H3K4me1标记。与自体产生IL-10的单核细胞不同，在健康受试者或黑色素瘤患者的静止或活化中性粒细胞的IL-10位点未检测到任何被评估的标记。相比之下，在小鼠中性粒细胞IL-10位点的共链区域检测到H3K4me3、H4Ac、H3K4me1和H3K27Ac水平升高。总之，数据表明，与单核细胞或小鼠中性粒细胞不同，人类中性粒细胞不能开启IL-10基因，因为其位点处于非活性状态，可能反映了中性粒细胞特异性的发育结果。隐含地，数据也明确地解决了目前尚未解决的关于人类中性粒细胞产生IL-10的能力的问题。免疫学杂志，2013,19(1):121 - 125。
To identify the molecular basis of IL-10 expression in human phagocytes, we evaluated the chromatin modification status at their IL-10 genomic locus. We analyzed posttranslational modifications of histones associated with genes that are active, repressed, or poised for transcriptional activation, including H3K4me3, H4Ac, H3K27Ac, and H3K4me1 marks. Differently from autologous IL-10-producing monocytes, none of the marks under evaluation was detected at the IL-10 locus of resting or activated neutrophils from healthy subjects or melanoma patients. By contrast, increased H3K4me3, H4Ac, H3K4me1, and H3K27Ac levels were detected at syntenic regions of the IL-10 locus in mouse neutrophils. Altogether, data demonstrate that human neutrophils, differently from either monocytes or mouse neutrophils, cannot switch on the IL-10 gene because its locus is in an inactive state, likely reflecting a neutrophil-specific developmental outcome. Implicitly, data also definitively settle a currently unsolved issue on the capacity of human neutrophils to produce IL-10. The Journal of Immunology, 2013, 190: 1921-1925.