抑制性受体结合ANGPTLs并支持血液干细胞和白血病的发展
Junke Zheng1, Masato Umikawa, Changhao Cui
1Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|June 5, 2012
概括
免疫抑制受体,人类白细胞免疫球蛋白样受体B2 (LILRB2) 和配对免疫球蛋白样受体 (PIRB),结合血管类蛋白质 (ANGPTLs). 这种相互作用支持成人干细胞活性和白血病的发展.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 通过表面受体通过环境线索对成年干细胞和癌细胞活动的调节尚不清楚.
- 已知血管类蛋白质 (ANGPTLs) 支持造血干细胞 (HSC) 活性,但由于缺乏已知的受体,它们被认为是孤儿配体.
- ANGPTLs还在脂质代谢,血管生成和炎症中发挥作用.
研究的目的:
- 为了识别血管类蛋白质 (ANGPTLs) 的受体.
- 研究这些受体在成人干细胞维护和癌症发展中的作用.
主要方法:
- 通过生物化学和细胞分析,确定LILRB2和PIRB作为ANGPTLs的受体.
- 对人类和小鼠的高细胞LILRB2和PIRB表达的分析.
- 评估ANGPTL与LILRB2/PIRB的结合及其对HSC扩张的作用.
- 在小鼠急性髓性白血病模型中评估PIRB信号传递的作用.
主要成果:
- 人类白细胞免疫球蛋白样受体B2 (LILRB2) 和它的小鼠正义对联免疫球蛋白样受体 (PIRB) 被确定为几个ANGPTL的受体.
- ANGPTL与LILRB2和PIRB的结合支持了高细胞的体外扩张.
- 在小鼠急性髓性白血病模型中,PIRB细胞内信号的缺陷导致白血病细胞分化增加,表明PIRB支持白血病的发展.
结论:
- 经典的免疫抑制受体,LILRB2和PIRB,在维持正常成年干细胞的干细胞性方面发挥了意想不到的作用.
- 这些受体还在支持癌症发展方面发挥作用,特别是在急性髓性白血病中.
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