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Regulatory T cells promote the stemness of leukemia stem cells through IL10 cytokine-related signaling pathway
Leukemia ( IF 12.8 ) Pub Date : 2021-08-11 , DOI: 10.1038/s41375-021-01375-2
Yingxi Xu 1, 2 , Junli Mou 1, 2 , Ying Wang 1, 3 , Wei Zhou 4 , Qing Rao 1, 2 , Haiyan Xing 1, 2 , Zheng Tian 1, 2 , Kejing Tang 1, 2 , Min Wang 1, 2 , Jianxiang Wang 1, 2, 3
Affiliation  

Regulatory T cells (Tregs) could maintain the characteristics of stem cells and inhibit the differentiation of normal hematopoietic stem/progenitor cells. Recent studies have shown that Tregs, as an important component of acute myeloid leukemia (AML) microenvironments, can help AML cells to evade immune surveillance. However, their function in directly regulating the stemness of AML cells remains elusive. In this study, the increased stemness of AML cells promoted by Tregs was verified in vitro and in vivo. The cytokines released by Tregs were explored, the highly expressed anti-inflammatory cytokine IL10 was found, which could promote the stemness of AML cells through the activation of PI3K/AKT signal pathway. Moreover, disrupting the IL10/IL10R/PI3K/AKT signal in AML/ETO c-kitmut (A/Ec) leukemia mice could prolong the mice survival and reduce the stemness of A/Ec leukemia cells. Finally, it was confirmed in patient samples that the proportion of Tregs to leukemia stem cells (LSCs) was positively correlated, and in CD34+ primary AML cells, the activation of PI3K/AKT was stronger in patients with high Tregs’ infiltration. After rhIL10 treatment, primary AML cells showed increased activation of PI3K/AKT signaling. Therefore, blocking the interaction between Tregs and AML cells may be a new approach to target LSCs in AML treatment.



中文翻译:

调节性T细胞通过IL10细胞因子相关信号通路促进白血病干细胞的干细胞性

调节性T细胞(Tregs)可以维持干细胞的特性,抑制正常造血干/祖细胞的分化。最近的研究表明,Tregs 作为急性髓性白血病 (AML) 微环境的重要组成部分,可以帮助 AML 细胞逃避免疫监视。然而,它们在直接调节 AML 细胞干性方面的功能仍然难以捉摸。在这项研究中,在体外和体内验证了 Tregs 促进的 AML 细胞干性增加。探索了Tregs释放的细胞因子,发现了高表达的抗炎细胞因子IL10,它可以通过激活PI3K/AKT信号通路促进AML细胞的干性。此外,破坏 AML/ETO c-kit mut中的 IL10/IL10R/PI3K/AKT 信号(A/Ec)白血病小鼠可以延长小鼠存活期,降低A/Ec白血病细胞的干性。最后,在患者样本中证实,Tregs 与白血病干细胞 (LSCs) 的比例呈正相关,并且在 CD34 +原代 AML 细胞中,高 Tregs 浸润的患者对 PI3K/AKT 的激活更强。在 rhIL10 处理后,原代 AML 细胞显示出 PI3K/AKT 信号的激活增加。因此,阻断 Tregs 与 AML 细胞之间的相互作用可能是 AML 治疗中靶向 LSCs 的一种新方法。

更新日期:2021-08-12
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