CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation.

Journal Article (Journal Article)

Hematopoietic stem and progenitor cells (HSPCs) depend on regulatory cytokines from the marrow microenvironment. From an unbiased cytokine screen of murine marrow supernatants, we identified C-C motif chemokine ligand 5 (CCL5) as an endothelial cell-secreted hematopoietic growth factor. Following treatment with CCL5, hematopoietic regeneration is accelerated and survival is prolonged after radiation. In mice with deletion of Ccr5, hematopoietic regeneration is delayed compared to control mice. Deletion of Ccr5 specifically in hematopoietic cells was sufficient to delay regeneration, while the deletion of Ccr5 in stromal/endothelial cells was not. Mechanistically, CCL5 promotes hematopoietic cell cycling and cell survival. Like murine hematopoietic cells, human hematopoietic cells (cord blood, healthy marrow, and peripheral blood) increase CCR5 expression after radiation exposure to promote cell survival. These data establish that CCL5 and CCR5 signaling play critical roles in hematopoietic regeneration and could serve as therapeutic targets to shorten the duration of myelosuppression.

Full Text

Duke Authors

Cited Authors

  • Piryani, SO; Kam, AYF; Vu, UT; Chao, NJ; Doan, PL

Published Date

  • July 9, 2019

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 76 - 90

PubMed ID

  • 31155503

Pubmed Central ID

  • PMC6626871

Electronic International Standard Serial Number (EISSN)

  • 2213-6711

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2019.04.023

Language

  • eng

Conference Location

  • United States