Jiang Xiao-Xia, Liu Yu, Li Hong, Gao Yaping, Mu Rong, Guo Jianping, Zhang Jing, Yang Yan-Mei, Xiao Fengjun, Liu Bing, Wang Changyong, Shen Beifen, Chen Si-Yi, Li Zhanguo, Yang Guang
Beijing Institute of Basic Medical Sciences, Beijing, China.
Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
Oncotarget. 2016 Oct 18;7(42):68086-68096. doi: 10.18632/oncotarget.11738.
The aberrant expansion of B1a cells has been observed in several murine autoimmune disease models; however, the mechanism of such proliferation of B1a cells is still limited. Here, we identify that Myb Like, SWIRM And MPN Domains 1 (MYSM1), a histone H2A deubiquitinase, plays an intrinsic role in the proliferation of B1a cells where MYSM1 deficiency results in the increased proliferation of B1a cells in mice. We demonstrate that MYSM1 recruits c-Myc to the promoter of miR-150 and stimulates the transcription of miR-150. Our further investigation shows that miR-150 decreases FMS-like tyrosine kinase 3 (FLT3) in B1a cells. In agreement with our animal studies, the percentage of FLT3+ B1 cells in Systemic Lupus Erythematosus (SLE) patients is significantly higher than healthy control. Thus, this study uncovers a novel pathway MYSM1/miR-150/FLT3 that inhibits proliferation of B1a, which may be involved in the pathogenesis of SLE.
在几种小鼠自身免疫性疾病模型中已观察到B1a细胞的异常扩增；然而，B1a细胞这种增殖的机制仍然有限。在此，我们发现组蛋白H2A去泛素化酶Myb样、SWIRM和MPN结构域1（MYSM1）在B1a细胞增殖中起内在作用，其中MYSM1缺陷导致小鼠B1a细胞增殖增加。我们证明MYSM1将c-Myc募集到miR-150的启动子并刺激miR-150的转录。我们的进一步研究表明，miR-150降低了B1a细胞中的FMS样酪氨酸激酶3（FLT3）。与我们的动物研究一致，系统性红斑狼疮（SLE）患者中FLT3+B1细胞的百分比显著高于健康对照。因此，本研究揭示了一条抑制B1a增殖的新型途径MYSM1/miR-150/FLT3，其可能参与SLE的发病机制。
