Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments
Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments
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Lnc-chop 促进肿瘤和炎症环境中骨髓源性抑制细胞的免疫抑制功能
DOI：
10.4049/jimmunol.1701721
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发表时间：
2018-04-15
影响因子：
4.4
通讯作者：
Yang, Rongcun
中科院分区：
文献类型：
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作者：
Gao, Yunhuan;Wang, Tiantian;Yang, Rongcun
骨髓源性抑制细胞（MDSC）是癌症免疫反应的主要调节因子。C/EBP同源蛋白（CHOP）和C/EBPβ在调节MDSC的免疫抑制功能中起着重要作用。在这项研究中，我们在MDSC中发现了一种称为lnc-chop的新型长非编码RNA，它可能与CHOP和C/EBPβ亚型肝脏富集抑制蛋白相互作用。lnc-chop与CHOP和C/EBPβ异构体肝脏富集抑制蛋白的结合促进了C/EBPβ的活化，并上调了与MDSC在炎症和肿瘤环境中的免疫抑制功能相关的抑制酶-1、NO合成酶2、NADPH氧化酶2和环氧合酶-2的表达。此外，lnc-chop还促进了H3 K4 me 3在脱氢酶-1、NO合酶2、NADPH氧化酶2和环氧合酶-2的启动子区域上的富集。这些发现表明lnc-chop在肿瘤环境中控制MDSC的免疫抑制功能中具有重要作用。
Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBPβ play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBPβ isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBPβ isoform liver-enriched inhibitory protein promoted the activation of C/EBPβ and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. Additionally, lnc-chop also promoted the enrichment of H3K4me3 on the promoter region of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2. These findings suggest an important role of lnc-chop in controlling immunosuppressive function of MDSCs in the tumor environment.