Endothelial microparticles delivering microRNA-155 into T lymphocytes are involved in the initiation of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng (+2 others)
2017 OncoTarget  
Endothelial microparticles (EMPs) upregulation has been observed in acute graftversus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and
more » ... icantly higher than the levels in plasma. Moreover, the rising peak of miR-155 in MPs occurred significantly prior to the peak in T lymphocytes. Additionally, we observed fluorescently-labeled miR-155 in EMPs actively transported into recipient T lymphocytes. Inhibition of miR-155 in EMPs by antagomir-155 did not influence the proliferation and apoptosis of T lymphocytes, but induced defective differentiation toward Th1, Th9 and Th17 cells and skewed differentiation toward Th2 and Treg cells. Furthermore, intravenous injection of miR-155-deficient-EMPs into aGVHD mice significantly attenuated the exacerbation of aGVHD manifestations and abnormal T lymphocytes differentiation induced by high concentration EMPs. Taken together, these data provide a mechanistic framework in which miR-155 delivered by EMPs is involved in aGVHD pathogenesis by activating specific T lymphocytes functions. The results may provide new therapeutic approaches for aGVHD while preserving graftversus-leukemia (GVL) effect.
doi:10.18632/oncotarget.15579 pmid:28423578 pmcid:PMC5410310 fatcat:zfmu4nsy5ram3ay2lnmupct7gy