JMJD3参与IFN-α和TLR7诱导的B细胞活化及凋亡

摘要

目的：探索组蛋白去甲基化酶JMJD3对B细胞活化和凋亡的影响。方法：磁珠分选纯化正常人及 SLE 患者外周血B细胞，用IFN-α、R848或IFN-α+R848处理纯化的B细胞，流式细胞仪检测CD86+或CD69+的细胞百分率以及CD86+Annexin V+或CD69+Annexin V+的细胞百分率；实时定量PCR和Western blot方法检测JMJD3的表达。结果：获得的B细胞纯度高达95％；IFN-α能够增强TLR7对B细胞的活化和凋亡；IFN-α也增加TLR7信号诱导的B细胞表达JMJD3，且JMJD3高表达依赖于MAPK通路，而不是NF-κB信号通路；SLE患者外周血B细胞高表达JMJD3，且JMJD3抑制剂能够抑制IFN-α+R848诱导的CD19+B细胞活化及凋亡。结论：JMJD3参与IFN-α和TLR7诱导的B细胞活化及凋亡，提示 JMJD3抑制剂可能具有缓解SLE症状的作用。%Objective:To explore the effect of histone demethylase JMJD3 on B cell activation and apoptosis.Methods:B cells were sorted and purified from the peripheral blood of healthy people and SLE patients by using magnetic bead.After B cells were treated with IFN-αor R848 or IFN-α+R848,the percentages of CD86+B cells,CD69+B cells,CD86+Annexin V+B cells and CD69+Annexin V+B cells were detected by flow cytometry.The expression of JMJD3 was detected by Real Time PCR and Western blot.Results:The purity of sorted B cells was up to 95%.IFN-αenhanced both the activation and apoptosis and the JMJD3 expression of TLR7-activated B cells.The expression of JMJD3 was dependent on MAPK signal pathway,but not the NF-κB signaling pathway.Moreover,JMJD3 was highly expressed in B cells of peripheral blood from SLE patients compared to those from healthy people.Furthermore,JMJD3 inhibitors could inhibit the activation and apoptosis of IFN-αand R848 activated B cells.Conclusion:JMJD3 participated in the activation and apoptosis of IFN-αand TLR7-induced B cells, suggesting JMJD3 inhibitors may possess therapeutic effect for alleviating symptom of SLE.