机构:[1]Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.[2]Hematology Oncology Center, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China.医技科室职能科室临床流行病与循证医学中心血液中心首都医科大学附属北京儿童医院[3]Biostatistics Shared Resource, Siteman Cancer Center, Washington University School of Medicine, Saint Louis, Missouri, USA.
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.
基金:
National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL131655]; Taub Foundation Grants Program for MDS Research
第一作者机构:[1]Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
共同第一作者:
通讯作者:
通讯机构:[1]Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.[*1]Division of Oncology, Department of Medicine, 660 South Euclid Avenue, Campus Box 8007, St. Louis, Missouri 63110, USA.
推荐引用方式(GB/T 7714):
Zhang Jingzhu,Supakorndej Teerawit,Krambs Joseph R.,et al.Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking[J].JOURNAL OF CLINICAL INVESTIGATION.2019,129(7):2920-2931.doi:10.1172/JCI124829.
APA:
Zhang, Jingzhu,Supakorndej, Teerawit,Krambs, Joseph R.,Rao, Mahil,Abou-Ezzi, Grazia...&Link, Daniel C..(2019).Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking.JOURNAL OF CLINICAL INVESTIGATION,129,(7)