Granulocyte Colony-Stimulating Factor Induces Osteoblast Inhibition by B Lymphocytes and Osteoclast Activation by T Lymphocytes during Hematopoietic Stem/Progenitor Cell Mobilization
Granulocyte Colony-Stimulating Factor Induces Osteoblast Inhibition by B Lymphocytes and Osteoclast Activation by T Lymphocytes during Hematopoietic Stem/Progenitor Cell Mobilization
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粒细胞集落刺激因子在造血干/祖细胞动员过程中诱导 B 淋巴细胞抑制成骨细胞和 T 淋巴细胞激活破骨细胞
DOI：
10.1016/j.bbmt.2015.05.005
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发表时间：
2015-08-01
影响因子：
4.3
通讯作者：
Qiu, Lugui
中科院分区：
文献类型：
--
作者：
Li, Sidan;Li, Tianshou;Qiu, Lugui
在骨髓（BM）中，造血干细胞和祖细胞（HSPC）位于骨内膜成骨细胞附近的专门龛中。排出至外周血的HSPC广泛用于移植，并且最常用重组人粒细胞集落刺激因子（G-CSF）进行动员。然而，启动动员级联反应和骨重建的G-CSF的细胞靶点尚未完全了解。在这里，我们研究了T和B淋巴细胞是否调节骨龛和影响HSPC动员。我们使用T和B缺陷小鼠，以显示G-CSF诱导的HSPC动员与B淋巴细胞相关，但与T淋巴细胞相关性较差。此外，我们发现缺陷型B淋巴细胞阻止了G-CSF介导的成骨细胞破坏，进一步的研究表明，BM成骨细胞减少与动员一致，由BM B淋巴细胞dickkopf 1的表达升高诱导。BM T细胞还通过调节核因子-κ B配体/骨保护素受体激活因子（RANKL/OPG）轴参与G-CSF诱导的破骨细胞活化。这些数据提供了BM B和T淋巴细胞通过调节骨重建在G-CSF诱导的HSPC动员中发挥作用的证据。(C)2015年美国血液和骨髓移植协会。
In the bone marrow (BM), hematopoietic stem and progenitor cells (HSPCs) reside in specialized niches near osteoblast cells at the endosteum. HSPCs that egress to peripheral blood are widely used for transplant, and mobilization is most commonly performed with recombinant human granulocyte colony-stimulating factor (G-CSF). However, the cellular targets of G-CSF that initiate the mobilization cascade and bone remodeling are not completely understood. Here, we examined whether T and B lymphocytes modulate the bone niche and influence HSPC mobilization. We used T and B defective mice to show that G-CSF induced mobilization of HSPCs correlated with B lymphocytes but poorly with T lymphocytes. In addition, we found that defective B lymphocytes prevent G-CSF mediated osteoblast disruption, and further study showed BM osteoblasts were reduced coincident with mobilization, induced by elevated expression of dickkopf1 of BM B lymphocytes. BM T cells were also involved in G-CSF induced osteoclast activation by regulating the Receptor Activator of Nuclear Factor-kappa B Ligand/Osteoprotegerin (RANKL/OPG) axis. These data provide evidence that BM B and T lymphocytes play a role in G-CSF induced HSPC mobilization by regulating bone remodeling. (C) 2015 American Society for Blood and Marrow Transplantation.