G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling
| Autor: | Adam M. Greenbaum, Angela Herman, Matthew J. Christopher, Daniel C. Link, Jill R. Woloszynek, Laura G. Schuettpelz, Molly Romine, Joshua N. Borgerding, Priya K. Gopalan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
G-CSF Biology Granulopoiesis Article Mice Granulocyte Colony-Stimulating Factor medicine Animals Receptor Toll-like receptor Toll-Like Receptors Hematopoietic stem cell hemic and immune systems Hematology Hematopoietic Stem Cells Cell biology Intestines Mice Inbred C57BL TLR2 Haematopoiesis medicine.anatomical_structure fms-Like Tyrosine Kinase 3 Oncology inflammation Myeloid Differentiation Factor 88 Receptors Granulocyte Colony-Stimulating Factor Immunology TLR4 toll-like receptor hematopoietic stem cell Stem cell Signal Transduction |
| Zdroj: | Leukemia |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/leu.2014.68 |
| Popis: | Recent studies demonstrate that inflammatory signals regulate hematopoietic stem cells (HSCs). Granulocyte-colony stimulating factor (G-CSF) is often induced with infection and plays a key role in the stress granulopoiesis response. However, its effects on HSCs are less clear. Herein, we show that treatment with G-CSF induces expansion and increased quiescence of phenotypic HSCs, but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor (TLR) expression and signaling. The G-CSF-mediated expansion of HSCs is reduced in mice lacking TLR2, TLR4 or the TLR signaling adaptor MyD88. Induction of HSC quiescence is abrogated in mice lacking MyD88 or in mice treated with antibiotics to suppress intestinal flora. Finally, loss of TLR4 or germ free conditions mitigates the G-CSF-mediated HSC repopulating defect. These data suggest that low level TLR agonist production by commensal flora contributes to the regulation of HSC function and that G-CSF negatively regulates HSCs, in part, by enhancing TLR signaling. |
| Databáze: | OpenAIRE |
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