title: MYSM1/miR-150/FLT3 inhibits B1a cell proliferation.
abstract: 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.
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors: Xiao-Xia
authors: XX
authors: Jiang
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.|Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
authors: Yu
authors: Y
authors: Liu
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors: Hong
authors: H
authors: Li
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors: Yaping
authors: Y
authors: Gao
authors: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
authors: Rong
authors: R
authors: Mu
authors: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
authors: Jianping
authors: J
authors: Guo
authors: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
authors: Jing
authors: J
authors: Zhang
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors: Yan-Mei
authors: YM
authors: Yang
authors: Institute of Radiation Medicine, Beijing, China.
authors: Fengjun
authors: F
authors: Xiao
authors: 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
authors: Bing
authors: B
authors: Liu
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors: Changyong
authors: C
authors: Wang
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Beifen
authors: B
authors: Shen
authors: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Si-Yi
authors: SY
authors: Chen
authors: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
authors: Zhanguo
authors: Z
authors: Li
authors: Beijing Institute of Basic Medical Sciences, Beijing, China.|State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Guang
authors: G
authors: Yang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D010450:Endopeptidases; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D014157:Transcription Factors; D064570:Ubiquitin-Specific Proteases; D051941:fms-Like Tyrosine Kinase 3; C533097:MIR150, human; C520745:MYSM1 protein, human; C497970:FLT3 protein, human; C570173:MYSM1 protein, mouse
keywords: B1a; FLT3; MYSM1; miR-150; proliferation