Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China.
Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
J Immunol. 2022 Oct 1;209(7):1401-1413. doi: 10.4049/jimmunol.2200195. Epub 2022 Aug 29.
Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity that regulate immune responses in the tumor microenvironment. We identified a novel long noncoding RNA (lncRNA), named as , in the MDSCs that controls their immunosuppressive functions. was induced in in vitro and in vivo inflammatory settings and upregulated the genes related to MDSC-mediated immunosuppression, including , , , and Furthermore, can not only bind with the C/EBPβ isoform liver-enriched activator protein to activate C/EBPβ but also with the methyltransferase WD repeat-containing protein 5 that enables the enrichment of histone H3 trimethylated lysine 4 marks on the promoter regions of , , , and , eventually resulting in their transcriptional activation. Furthermore, the conserved human has a similar function as murine Taken together, upregulation of in the tumor microenvironment promotes the immunosuppressive function of MDSCs.
髓系来源的抑制性细胞（MDSCs）是一种具有强大免疫抑制活性的病理性激活的中性粒细胞和单核细胞，能够调节肿瘤微环境中的免疫反应。我们在 MDSCs 中鉴定出一种新型长非编码 RNA（lncRNA），命名为 ，它能够控制 MDSC 的免疫抑制功能。在体外和体内炎症环境中诱导产生 ，并上调与 MDSC 介导的免疫抑制相关的基因，包括 、 、 、 。此外， 不仅可以与富含 C/EBPβ 同工型的肝激活蛋白结合，激活 C/EBPβ，还可以与甲基转移酶 WD 重复蛋白 5 结合，使组蛋白 H3 赖氨酸 4 三甲基化标记在 、 、 、 启动子区域上的富集，最终导致它们的转录激活。此外，保守的人类 与小鼠 具有相似的功能。总之，肿瘤微环境中 的上调促进了 MDSC 的免疫抑制功能。
