Mitf 调节涉及 B 细胞恒温,生殖中心反应和耐受性相关的基因表达网络
Abhimanyu Amarnani1,2,3, Maria Lopez-Ocasio1,4, Ramile Dilshat5
1Program in Molecular and Cellular Biology, School of Graduate Studies, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, United States.
微症转录因子 (Mitf) 调节B细胞耐受性和自身免疫力. 在B细胞中MITF缺乏导致腹壮大,自身抗体和狼性疾病,突出其关键作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 众所周知,微症转录因子 (Mitf) 影响B细胞激活和耐受性.
- 然而,特定的B细胞机制和与相关的MiT因子 (Tfe3,Tfeb,Tfec) 的区别尚不清楚.
研究的目的:
- 阐明Mitf和相关的MiT转录因子的B细胞特异性功能.
- 识别B细胞中由Mitf调节的新型基因和途径.
主要方法:
- 使用了两种小鼠模型:Mitf系统性功能丧失和B细胞特异性MiT家族失活.
- 在体外休息的B细胞上使用RNA测序 (RNAseq) 来分析转录变化.
主要成果:
- 这两种模型都表现出大,血细胞增加,自身抗体和蛋白尿.
- 在B细胞中MiT无活化加剧了狼类自身免疫性疾病.
- RNAseq揭示了参与细胞周期,生殖中心反应和血细胞分化的基因的上调,包括Socs6,Isp53,S1pR2和IgG2b/c.
结论:
- Mitf是B细胞内在生殖中心程序的关键调节者,通过新的基因影响自我耐受.
- Mitf还调节影响B细胞微环境的全身炎症,与其他MiT因素不同.
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