Dahlin Joakim S, Ekoff Maria, Grootens Jennine, Löf Liza, Amini Rose-Marie, Hagberg Hans, Ungerstedt Johanna S, Olsson-Strömberg Ulla, Nilsson Gunnar
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, and.
Blood. 2017 Oct 19;130(16):1785-1794. doi: 10.1182/blood-2017-03-773374. Epub 2017 Aug 8.
Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.
一般认为，人类造血祖细胞在分化形成肥大细胞的过程中需要干细胞因子（SCF）和KIT信号传导。抑制KIT信号传导的伊马替尼治疗可在体内耗尽肥大细胞。此外，缺乏SCF或进行伊马替尼治疗会阻止祖细胞在体外发育成肥大细胞。然而，这些观察结果并不意味着肥大细胞祖细胞在整个分化过程中都需要SCF和KIT信号传导。在这里，我们证明接受伊马替尼治疗的患者体内存在循环肥大细胞祖细胞。此外，我们表明外周血中的肥大细胞祖细胞在体外无需SCF和KIT信号传导即可存活、成熟和增殖。与普遍的共识相反，我们的结果表明SCF和KIT信号传导对于早期肥大细胞发育并非必需。
