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

Xin-Jiang Lu, Qiang Chen, Ye-Jing Rong, Guan-Jun Yang, Chang-Hong Li, Ning-Yi Xu, Chao-Hui Yu, Hui-Ying Wang, Shun Zhang, Yu-Hong Shi and Jiong Chen ()
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Xin-Jiang Lu: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Qiang Chen: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Ye-Jing Rong: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Guan-Jun Yang: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Chang-Hong Li: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Ning-Yi Xu: Life Sciences Institute, Zhejiang University
Chao-Hui Yu: the First Affiliated Hospital, School of Medicine, Zhejiang University
Hui-Ying Wang: the Second Affiliated Hospital, School of Medicine, Zhejiang University
Shun Zhang: Clinical Research Center, Ningbo No. 2 Hospital
Yu-Hong Shi: Laboratory of Biochemistry and Molecular Biology, Ningbo University
Jiong Chen: Laboratory of Biochemistry and Molecular Biology, Ningbo University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms12719

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