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

• Published in: Nature communications 2016-09, Vol.7 (1), p.12719-12719, Article 12719
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 631/250/127; 631/532/1542; Animals; Bone marrow; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Lineage - physiology; CHO Cells; Cricetulus; Cytokines; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Homeostasis; Humanities and Social Sciences; Humans; Intercellular Signaling Peptides and Proteins - pharmacology; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Leukocytes; Leukocytes, Mononuclear; Life sciences; Macrophages - drug effects; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recombinant Proteins - pharmacology; Science; Science (multidisciplinary); Stem cells; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12719

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. How extramedullar cytokines regulate hematopoietic stem cell (HSC) homeostasis is unclear. Here, the authors show that the cytokine leukocyte cell-derived chemotaxin 2 regulates HSC expansion and mobilisation via tumour necrosis factor and interaction with CD209a in macrophages.