Study On The Role Of LINC01882 In The Pathogenesis Of AGVHD Through Regulating T Cells Function

Objective:Hematopoietic stem cell transplantation is an effective way to cure hematological diseases.However,acute graft-versus-host disease is a major complication after transplantation,which limits its wide clinical application.The occurrence of aGVHD is closely related to T cells.Studies have shown that non-coding RNA-microRNA plays an important role in the occurrence of aGVHD.For example,our previous experiments in vivo and in vitro confirmed that microRNA-155 could promote T cells to differentiate into Th1,Th9 and Th17 cells,inhibit the differentiation to Th2 and Treg cells,and participate in progress of aGVHD.In recent years,many studies have shown that another kind of non-coding RNA-lncRNA plays an essential role in regulating the differentiation of T cells,but there are no reports about the role of lncRNA in the development of aGVHD.LINC01882 molecule is a newly discovered lncRNA,which is mainly expressed in T cells and plays an important role in the differentiation and activation of T cells.In order to explore the role of lncRNA in aGVHD,the function of LINC01882 molecule was studied.Methods:1.qRT-PCR was used to detect the expression of LINC01882,ZEB1 and PDE7A in CD3~+T cells of human peripheral blood which were activated by PHA or anti-CD3/CD28.LINC01882,ZEB1,and PDE7A were detected by the same way in control group.2.CD3~+T cells which were extracted from peripheral blood by magnetic beads were collected from patients with aGVHD and those without aGVHD.The expression of LINC01882 was detected by qRT-PCR.3.LINC01882 overexpression lentiviral vector was constructed.The expression levels of LINC01882,ZEB1,PDE7A and miR-155 genes were detected by qRT-PCR,T cell subsets were detected by flow cytometry,and T cell proliferation was detected by CCK8.4.LINC01882 siRNA was transfected into CD3~+T cells by lipo3000.The expression levels of LINC01882,ZEB1,PDE7A and microRNA-155 were detected by qRT-PCR after cultured for 48 hours.Results:1.Compared with the control group,the expression levels of LINC01882,ZEB1,and PDE7A were significantly down-regulated in CD3~+T cells after stimulation with PHA or CD3/CD28.2.Compared with patients without aGVHD,the expression level of LINC01882 in T cell from peripheral blood of aGVHD patients was down-regulated after allogeneic hematopoietic stem cell transplantation.3.The level of microRNA-155 was up-regulated in LINC01882 over-expressed CD3~+T cells.And the over-expression of LINC01882 could inhibit T cell proliferation,and decrease the proportion of CD8~+T cell.4.The expression of ZEB1,PDE7A and miR-155 were down-regulated in LINC01882knocked down CD3~+T cells.Conclusion:1.LINC01882 participated in the activation of T cells and could regulate the gene expression of ZEB1 and PDE7A in T cells.2.LINC01882 participated in the occurrence of aGVHD.3.LINC01882 could regulate the proliferation and induce the differentiation of T cells.4.LINC01882 could positively regulate the expression of microRNA-155 in CD3~+T cells.In conclusion,LINC01882 could regulate the differentiation and proliferation of T cells,and participate in the occurrence of aGVHD.However,there are still few studies on the function of LINC01882,and further studies of LINC01882 are needed to explore.