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.
Highlights
The mechanisms by which cytokines in the blood affect Haematopoietic stem cells (HSCs) homeostasis remain largely unknown
Because CD209a was mainly expressed in macrophages and osteolineage cells (Fig. 3h), we further investigated the effect of leukocyte cell-derived chemotaxin 2 (LECT2)/CD209a signal on tumour necrosis factor (TNF)
We demonstrated that recombinant LECT2 injection induced HSC expansion and mobilization
Summary
The mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. HSC expansion and mobilization are regulated by BM niche cells[3], including osteolineage cells (mature osteoblasts and osteoblast progenitors), macrophages, osteoclasts, endothelial cells, neutrophils, and mesenchymal stem and stromal cells. These BM niche cells can secrete a variety of growth factors or cytokines that affect HSC function[3,4,5,6,7], for examples, osteolineage cells produce granulocyte colony-stimulating factor (G-CSF)[8], the stromal cells that surround HSCs release stem cell factor[9] and endothelial cells produce E-selectin ligand to regulate HSC proliferation[10]. We propose that extramedullar cytokines in the blood regulate the BM niche to affect HSC expansion and mobilization
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