科研之友
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摘要
Bone marrow (BM) resident macrophages (M phi s) regulate hematopoietic stem cell (HSC) mobilization; however, their impact on HSC function has not been investigated. We demonstrate that depletion of BM resident M phi s increases HSC proliferation as well as the pool of quiescent HSCs. At the same time, during bacterial infection where BM resident M phi s are selectively increased we observe a decrease in HSC numbers. Moreover, strategies that deplete or reduce M phi s during infection prevent HSC loss and rescue HSC function. We previously found that the transient loss of HSCs during infection is interferon-gamma (IFN)-dependent. We now demonstrate that IFN signaling specifically in M phi s is critical for both the diminished HSC pool and maintenance of BM resident M phi s during infection. In addition to the IFN-dependent loss of BM HSC and progenitor cells (HSPCs) during infection, IFN reduced circulating HSPC numbers. Importantly, under infection conditions AMD3100 or G-CSF-induced stem cell mobilization was impaired. Taken together, our data show that IFN acts on M phi s, which are a negative regulator of the HSC pool, to drive the loss in BM and peripheral HSCs during infection. Our findings demonstrate that modulating BM resident M phi numbers can impact HSC function in vivo, which may be therapeutically useful for hematologic conditions and refinement of HSC transplantation protocols. Stem Cells 2015;33:2294-2305
- 出版日期2015-7
