Paracrine CCL17 and CCL22 signaling regulates hematopoietic stem/progenitor cell migration and retention in mouse fetal liver

Biochem Biophys Res Commun. 2020 Jun 30;527(3):730-736. doi: 10.1016/j.bbrc.2020.04.045. Epub 2020 May 18.

Abstract

Fetal liver (FL) is the major embryonic hematopoietic organ and a site where circulating hematopoietic stem/progenitor cells (HSPCs) reside. However, HSPC migration/retention mechanisms in FL remain unclear. A chemokine screen revealed that the CCR4 ligands CCL17 and CCL22 are highly expressed in mouse embryonic day (E) 12.5 FL. Flow cytometric analysis confirmed CCR4 expression in FL HSPCs. To identify sources of CCL17 and CCL22, we fractionated FL into various cell types and found that Ccl17 and Ccl22 were predominantly expressed in HPCs/matured HCs. In vitro cell migration analysis confirmed enhanced HSPC migration in the presence of HPCs/matured HCs. Furthermore, exo-utero injection of anti-CCR4 neutralizing antibody into pregnant mice significantly reduced the number of FL HSPCs in embryos. These data demonstrate a paracrine mechanism by which HSPC migration/retention is regulated by CCL17 and CCL22 secreted from HPCs or matured HCs in FL.

Keywords: CCL17; CCL22; CCR4; Hematopoietic stem cell; Migration; Paracrine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cells, Cultured
  • Chemokine CCL17 / metabolism*
  • Chemokine CCL22 / metabolism*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Liver / cytology
  • Liver / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Paracrine Communication
  • Signal Transduction*

Substances

  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22