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

Nat Commun. 2016 Sep 6;7:12719. doi: 10.1038/ncomms12719.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Lineage / physiology*
  • Cricetulus
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Granulocyte Colony-Stimulating Factor
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Leukocytes, Mononuclear
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Intercellular Signaling Peptides and Proteins
  • Lect2 protein, mouse
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor