Regulation Of Long Non-coding RNA AK124826 On Th17/Treg Cell Balancein Patient With Polymyositis/Dermatomysitis

Polymyositis/dermatomyositis(PM/DM)are systemic autoimmune diseases characterized by CD4~+T cells reaction are thought to be involved significantly in the pathogenesis.Recent work shown that Th17/Tregwasimbalance in the patients with PM/DM,however,the molecular mechanisms under this abnormality were poorly understood.Study shown that long non-coding RNA AK124826 was significantly up-regulated in the CD4~+T cells from PM/DM patients,by contrast,IL-27 was down-regulated.In addition,the results from CHIP indicated that IL-27 was a target of lncRNA AK124826.Given that IL-27 was regarded as a critical regulator in the Th17/Treg differentiation,we hypotheses that lncRNA AK124826 regulate the expression of IL-27and thus been involved in the pathogenesis of PD/DM.To address this issue,the effect of lncRNA AK124826 on the Th17/Treg differentiation was investigated by"gain and loss of function".More importantly,whether IL-27 mediated the function of lncRNA AK124826in regulating Th17/Treg differentiation was explored.The present work will introduce us new insights into the pathogenesis ofPD/DM.Objective:To investigate the effect of lncRNA AK124826 on the balance of Th17/Treg cells through the target gene IL-27,and to participate in the development of PM/DM.Method:The expression of lncRNA AK124826,IL-17 and FoxP3 in peripheral blood CD4~+T cells was detected by real-time PCR.The percentage of Th17 cells and Treg cells in peripheral blood CD4~+T cells was detected by flow cytometry.The levels of IL-17,TGF-?and creatine kinase(CK)and IL-27 in serum were measured by ELISA.The lncRNAAK124826 lentiviral overexpression vector or RNAi lentiviral interference vector was transferred into the peripheral CD4~+CD45RA~+T cells of PM/DM patients,and stimulated with IL-6,TGF-?,autoantigen Jo-1 of PM/DM,The expression of Th17 and Treg cells was detected by flow cytometry.The effect of lncRNA AK124826 lentivirus overexpression and iRNA interference on JAK-STAT and MAPK/P38 signaling pathway was detected by Western-blot.Result:Compared with the healthy control group,the expression of TGF-?and CK in PM/DM patients was significantly increased(P<0.01),the expression of lncRNA AK124826 was significantly increased(P<0.01),while the expression of IL-17 was significantly increased(P<0.01),and FoxP3 gene expression was significantly decreased(P<0.01).The percentage of Th17 cells in peripheral blood CD4~+T cells of patients with PM/DM was(3.24±1.47)%,which was significantly higher than that in healthy controls(0.82±0.24)%(P<0.01);The percentage of Treg cells in peripheral blood CD4~+T cells of patients with PM/DM was(3.27±0.45)%,which was significantly lower than that of the control group(6.78±0.92)%(P<0.01);The expression level of IL-27 in peripheral blood of patients with PM/DM was 13.42±3.73 pg/ml,which was significantly lower than that of healthy controls 36.3±8.09 pg/ml(P<0.01).The proportion of Th17 cells in lncRNA AK124826 overexpression group was significantly increased,While Treg cells were significantly decreased;However,when the expression of lncRNAAK124826 was reduced,the proportion of Th17 cells was significantly decreased,Treg cells increased significantly.Conclusion:In the patients with PM/DM,the expression of lncRNA AK124826 was significantly increased,and the differentiation of Th17/Treg cells was regulated,LncRNA AK124826 promotes the differentiation of CD4~+CD45RA~+T cells into Th17 cells and inhibits its differentiation into Treg cells.LncRNA AK124826 is involved in the development of PM/DM by this mechanism.