LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells.

LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells.
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LECT2通过调节巨噬细胞和骨系细胞驱动造血干细胞扩张和动员

DOI:
10.1038/ncomms12719
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发表时间:
2016-09-06
影响因子:
16.6
通讯作者:
Chen, Jiong
Chen, Jiong
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lu, Xin-Jiang;Chen, Qiang;Rong, Ye-Jing;Yang, Guan-Jun;Li, Chang-Hong;Xu, Ning-Yi;Yu, Chao-Hui;Wang, Hui-Ying;Zhang, Shun;Shi, Yu-Hong;Chen, Jiong

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造血干细胞(HSCs)可以分化为血液中所有谱系的细胞。然而,血液中细胞因子影响HSC稳态的机制在很大程度上仍然未知。在这里,我们表明,白细胞来源的趋化因子2(LECT 2),一个多功能的细胞因子,诱导HSC的扩增和动员。重组LECT2给药导致HSC在骨髓中扩增并通过CD209a动员到血液中。在巨噬细胞特异性耗竭或成骨细胞减少后,LECT2对HSC的作用降低。LECT2治疗降低了巨噬细胞和成骨细胞中的肿瘤坏死因子(TNF)表达。在TNF敲除小鼠中,LECT2对HSC的作用降低。此外,LECT2诱导照射小鼠HSC动员,而粒细胞集落刺激因子没有。我们的研究结果表明,LECT 2是一种髓外细胞因子,有助于HSC的稳态,并可能有助于诱导HSC动员。
Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells. LECT2 treatment reduces the tumour necrosis factor (TNF) expression in macrophages and osteolineage cells. In TNF knockout mice, the effect of LECT2 on HSCs is reduced. Moreover, LECT2 induces HSC mobilization in irradiated mice, while granulocyte colony-stimulating factor does not. Our results illustrate that LECT2 is an extramedullar cytokine that contributes to HSC homeostasis and may be useful to induce HSC mobilization.
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发表时间: 2016-01-08
影响因子: 16.6
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