Granulocyte-derived TNF α promotes vascular and hematopoietic regeneration in the bone marrow

Nature Medicine 24, 95 (2018). doi:10.1038/nm.4448 Authors: Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello & Daniel Lucas Endothelial cells are a critical component of the bone marrow (BM) stromal network, which maintains and regulates hematopoietic cells. Vascular regeneration precedes, and is necessary for, successful hematopoietic stem cell (HSC) transplantation, the only cure for most hematopoietic diseases. Recent data suggest that mature hematopoietic cells regulate BM stromal-cell function. Whether a similar cross-talk regulates the BM vasculature is not known. Here we found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after BM transplantation in mice. Adoptive transfer of BM, but not peripheral, granulocytes prevented the death of mice transplanted with limited numbers of HSCs and accelerated recovery of host vessels and hematopoietic cells. Moreover, selective granulocyte ablation in vivo impaired vascular and hematopoietic regeneration after BM transplantation. Gene expression analyses indicated that granulocytes are the main source of the cytokine TNFα, whereas its receptor TNFR1 is selectively upregulated in regenerating blood vessels. In adoptive transfer experiments, wild type, but not Tnfa−/−, granulocytes induced vascular recovery, and wild-type granulocyte transfer did not prevent death or promote vascular regeneration...
Source: Nature Medicine - Category: General Medicine Authors: Tags: Letter Source Type: research