Giampaolo Sabrina, Wójcik Gabriela, Serfling Edgar, Patra Amiya K
Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.
Institute of Translational and Stratified Medicine, Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth, UK.
Oncotarget. 2017 May 2;8(18):29625-29642. doi: 10.18632/oncotarget.16377.
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2-/- mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2-/- mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2-/- mice, preventing IFN-γ activity could do the same even in the absence of Treg cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.
白细胞介素-2（IL-2）在造血干细胞（HSC）维持中的作用尚不清楚。在此我们表明，Il2基因敲除小鼠在HSC维持方面出现严重异常，导致造血功能缺陷。然而，缺乏IL-2信号传导对淋巴细胞生成和红细胞生成有害，而在Il2基因敲除小鼠中髓细胞生成增强。对Il2基因敲除小鼠造血失调潜在机制的研究表明，IL-2-调节性T细胞（Treg）轴对于HSC维持和正常造血必不可少。Treg活性的缺乏导致活化T细胞产生的干扰素-γ（IFN-γ）增加以及骨髓（BM）中HSCs的扩增。虽然，恢复Treg群体成功挽救了Il2基因敲除小鼠的HSC维持，即使在没有Treg细胞的情况下，阻止IFN-γ活性也能达到同样效果。我们的研究表明，IL-2和IFN-γ活性的平衡对于稳态造血至关重要，并且在骨髓衰竭的临床情况下，IL-2或抗IFN-γ治疗可能有助于恢复造血。
