Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
By A. Chow, D. Lucas, A. Hidalgo, S. Méndez-Ferrer, D. Hashimoto, C. Scheiermann, M. Battista, M. Leboeuf, C. Prophete, N. Van Rooijen and 3 more. Journal of Experimental Medicine, 2011
833 citations recorded by the source corpus.
Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin+ niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169+ MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin+ niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.
Subfields: Hematology, Immunology
View Paper: https://www.semanticscholar.org/paper/75e9f5074d08c272ac8cf3424ab24356319729b9
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Citations in the corpus
- Tissue resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes (2013, background): “Administration of diphtheria toxin (DT) into CD169-DTR animals allows for specific depletion of certain tissue-resident macrophages without ablating monocytes or dendritic cells (Asano et al., 2011; Chow et al., 2011; Miyake et al., 2007).”
- Rhythmic modulation of the hematopoietic niche through neutrophil clearance (2013, positive): “Macrophages have been shown to support the function of the hematopoietic niche through the production of undefined protein factors (Chow et al., 2011; Winkler et al., 2010).”
- Much More than M1 and M2 Macrophages, There are also CD169+ and TCR+ Macrophages (2015, methodology): “They found that CD169+ macrophages from the BM promoted retention of the hematopoietic stem cells (HSC) by acting on the Nestin+ HCS, suggesting that G-CSF signaling in macrophages is sufficient to promote HSC mobilization (146).”
- Macrophage heterogeneity in tissues: phenotypic diversity and functions (2014, background): “This molecule has been implicated in controlling myeloid cell release from the bone marrow into the circulation (44).”