Zhao Xin, Huang Xiao-Hui, Dong Xiao-Hui, Wang Yu-Han, Yang Hui-Xin, Wang Yan, He Youdi, Liu Shuang, Zhou Jin, Wang Changyong, Jiang Xiao-Xia
Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
Department of Urology, First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, Heilongjiang, People's Republic of China.
Mol Biol Rep. 2018 Dec;45(6):2393-2401. doi: 10.1007/s11033-018-4405-3. Epub 2018 Nov 1.
Macrophages play pivotal roles in innate and adaptive immune response, tissue homeostasis and cancer development. Their development and heterogeneity are tightly controlled by epigenetic program and transcription factors. Deubiquitinase Mysm1 plays crucial roles in regulating stem cell maintenance and immune cell development. Here we show that Mysm1 expression is up regulated during bone marrow macrophage development. Mysm1 deficient cells exhibit accelerating proliferation with more cells going to S phase and higher cyclin D1, cyclin D2 and c-Myc expression. However, compared to WT counterparts, more cell death is also detected in Mysm1 deficient cells no matter M-CSF deprived or not. In LPS-condition medium, Mysm1 macrophages show more pro-inflammatory factors IL-1β, TNFα and iNOS production. In addition, much higher expression of surface marker CD86 is detected in Mysm1 macrophages. In vivo tumor model data demonstrate that in contrast to WT macrophages promoting tumor growth, Mysm1 macrophages inhibit tumor growth, showing the properties of M1 macrophages. Collectively, these data indicate that Mysm1 is essential for macrophage survival and plays an important role in macrophage polarization and might be a target for cell therapy.
巨噬细胞在先天性和适应性免疫反应、组织稳态及癌症发展中发挥着关键作用。它们的发育和异质性受到表观遗传程序和转录因子的严格控制。去泛素化酶Mysm1在调节干细胞维持和免疫细胞发育中起关键作用。在此我们表明，在骨髓巨噬细胞发育过程中Mysm1表达上调。Mysm1缺陷细胞表现出增殖加速，更多细胞进入S期，且细胞周期蛋白D1、细胞周期蛋白D2和c-Myc表达更高。然而，与野生型对应细胞相比，无论是否剥夺M-CSF，在Mysm1缺陷细胞中也检测到更多细胞死亡。在LPS条件培养基中，Mysm1巨噬细胞显示出更多促炎因子白细胞介素-1β、肿瘤坏死因子α和诱导型一氧化氮合酶的产生。此外，在Mysm1巨噬细胞中检测到表面标志物CD86的表达明显更高。体内肿瘤模型数据表明，与促进肿瘤生长的野生型巨噬细胞相反，Mysm1巨噬细胞抑制肿瘤生长，表现出M1巨噬细胞的特性。总体而言，这些数据表明Mysm1对巨噬细胞存活至关重要，在巨噬细胞极化中起重要作用，可能是细胞治疗的一个靶点。
