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

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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)

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.

Suggested Citation

  • 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 & Jiong Chen, 2016. "LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12719
    DOI: 10.1038/ncomms12719
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