Journal article
Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking
The Journal of clinical investigation, Vol.129(7), pp.2920-2931
07/01/2019
DOI: 10.1172/JCI124829
PMCID: PMC6597218
PMID: 31039135
Abstract
A resident population of dendritic cells (DCs) has been identified in murine bone marrow, but its contribution to the regulation of hematopoiesis and establishment of the stem cell niche is largely unknown. Here, we show that murine bone marrow DCs are perivascular and have a type 2 conventional DC (cDC2) immunophenotype. RNA expression analysis of sorted bone marrow DCs showed that expression of many chemokines and chemokine receptors is distinct from that observed in splenic cDC2s, suggesting that bone marrow DCs might represent a unique DC population. A similar population of DCs was present in human bone marrow. Ablation of conventional DCs (cDCs) results in hematopoietic stem/progenitor cell (HSPC) mobilization that was greater than that seen with ablation of bone marrow macrophages, and cDC ablation also synergizes with granulocyte–colony stimulating factor to mobilize HSPCs. Ablation of cDCs was associated with an expansion of bone marrow endothelial cells and increased vascular permeability. CXCR2 expression in sinusoidal endothelial cells and the expression of 2 CXCR2 ligands, CXCL1 and CXCL2, in the bone marrow were markedly increased following cDC ablation. Treatment of endothelial cells in vitro with CXCL1 induced increased vascular permeability and HSPC transmigration. Finally, we showed that HSPC mobilization after cDC ablation is attenuated in mice lacking CXCR2 expression. Collectively, these data suggest that bone marrow DCs play an important role in regulating HSPC trafficking, in part, through regulation of sinusoidal CXCR2 signaling and vascular permeability.
Details
- Title: Subtitle
- Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking
- Creators
- Jingzhu Zhang - Washington University in St. LouisTeerawit Supakorndej - Washington University in St. LouisJoseph R. Krambs - Washington University in St. LouisMahil Rao - Washington University in St. LouisGrazia Abou-Ezzi - Washington University in St. LouisRachel Y. Ye - Washington University in St. LouisSidan Li - Washington University in St. LouisKathryn Trinkaus - Washington University in St. LouisDaniel C. Link - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.129(7), pp.2920-2931
- DOI
- 10.1172/JCI124829
- PMID
- 31039135
- PMCID
- PMC6597218
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Number of pages
- 12
- Grant note
- RO1HL131655 (DCL) / National Institute of Health Program for MDS Research Grant / ;
- Language
- English
- Date published
- 07/01/2019
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics
- Record Identifier
- 9984775275002771
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