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

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.

CXCR3.1 and CXCR3.2 Differentially Contribute to Macrophage Polarization in Teleost Fish

“…15B). Sepsis is characterized by inefficient bacterial clearance and the overexpression of inflammatory cytokines (38,42). Therefore, we examined the effects of macrophage infusion on the bacterial burden and cytokine production during L. anguillarum-induced sepsis.…”

Extracellular molecules in hematopoietic stem cell mobilisation

“…Disruption of CXCL12 binding to CXCR4 is a common feature of mobilization strategies, occurring in G-CSF, Flt-3L, SCF, LECT2, plerixafor, and chemotherapy-driven mechanisms [36][37][38]. The importance of the loss of CXCL12/CXCR4 interactions in G-CSF-mediated mobilization is highlighted by the complete absence of G-CSF induced mobilization in CXCR4 −/− bone marrow chimeric mice [37].…”

Cytokine‐induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

“…61 Macrophages also play a role in HSPC mobilization induced by leukocyte cell-derived chemotaxin 2 (LECT2), as the LECT2 receptor (CD209a) is mainly expressed on macrophages and osteolineage cells. 62 Together, these results unequivocally point to a role for macrophages in HSPC mobilization. However, more research is needed to delineate the nature of the involved macrophage subpopulations.…”