CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation
Summary: 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. Fol...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671119301456 |
| _version_ | 1818529815650631680 |
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| author | Sadhna O. Piryani Angel Y.F. Kam Uyen T. Vu Nelson J. Chao Phuong L. Doan |
| author_facet | Sadhna O. Piryani Angel Y.F. Kam Uyen T. Vu Nelson J. Chao Phuong L. Doan |
| author_sort | Sadhna O. Piryani |
| collection | DOAJ |
| description | Summary: 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. : CC-chemokine receptor 5 (CCR5) may be best known as a co-receptor for HIV, but its role in hematopoiesis is incompletely defined. Using a combination of transplantation studies, genetic murine models, and human specimens, Doan and colleagues demonstrate that CCL5/CCR5 signaling promotes hematopoietic regeneration in response to myelosuppressive radiation injury. Keywords: hematopoietic stem cell, endothelial cell, CCL5, CCR5, RANTES, regeneration, hematopoietic growth factor, hematopoietic cytokine, hematopoietic microenvironment, vascular niche |
| first_indexed | 2024-12-11T17:11:46Z |
| format | Article |
| id | doaj.art-6d076978ac47434ca6da9a682b822314 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-11T17:11:46Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-6d076978ac47434ca6da9a682b8223142022-12-22T00:57:30ZengElsevierStem Cell Reports2213-67112019-07-011317690CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing RadiationSadhna O. Piryani0Angel Y.F. Kam1Uyen T. Vu2Nelson J. Chao3Phuong L. Doan4Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC 27710, USADivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC 27710, USADivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC 27710, USADivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC 27710, USA; Duke Cancer Institute, Duke University, 595 LaSalle Street, DUMC 103866, Durham, NC 27710, USADivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC 27710, USA; Duke Cancer Institute, Duke University, 595 LaSalle Street, DUMC 103866, Durham, NC 27710, USA; Corresponding authorSummary: 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. : CC-chemokine receptor 5 (CCR5) may be best known as a co-receptor for HIV, but its role in hematopoiesis is incompletely defined. Using a combination of transplantation studies, genetic murine models, and human specimens, Doan and colleagues demonstrate that CCL5/CCR5 signaling promotes hematopoietic regeneration in response to myelosuppressive radiation injury. Keywords: hematopoietic stem cell, endothelial cell, CCL5, CCR5, RANTES, regeneration, hematopoietic growth factor, hematopoietic cytokine, hematopoietic microenvironment, vascular nichehttp://www.sciencedirect.com/science/article/pii/S2213671119301456 |
| spellingShingle | Sadhna O. Piryani Angel Y.F. Kam Uyen T. Vu Nelson J. Chao Phuong L. Doan CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation Stem Cell Reports |
| title | CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation |
| title_full | CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation |
| title_fullStr | CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation |
| title_full_unstemmed | CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation |
| title_short | CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation |
| title_sort | ccr5 signaling promotes murine and human hematopoietic regeneration following ionizing radiation |
| url | http://www.sciencedirect.com/science/article/pii/S2213671119301456 |
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