滤泡调节性T细胞减少与类风湿性关节炎发生和发展相关

Reduction of follicular regulatory T cells is associated with occurrence and development of rheumatoid arthritis

目的探讨滤泡调节性T(Tfr)细胞在类风湿性关节炎(RA)发病中的可能机制。方法采用流式细胞术检测20例RA患者及20例健康体检者外周血中CD4^(+)CXCR5^(+)FOXP3^(+)ICOS^(+)Tfr细胞的百分比并分析Tfr细胞比例与RA临床实验室检测指标的相关性;ELISA检测患者血清中白细胞介素10(IL-10)、IL-12、IL-2、转化生长因子β(TGF-β)、CXC趋化因子配体13(CXCL13)的水平;实时定量PCR检测外周血单个核细胞(PBMC)的B细胞淋巴瘤因子6(Bcl6)、B淋巴细胞诱导成熟蛋白1(Blimp-1)的mRNA表达;免疫组织化学法检测RA患者关节滑膜Bcl6、CXCL13的表达。结果与健康对照组相比,RA患者外周血Tfr细胞比例显著下降;Tfr细胞百分比与C反应蛋白(CRP)、类风湿因子(RF)、血沉(ESR)、28关节疾病活动度评分(DAS28)水平呈负相关;RA患者血清中IL-12、CXCL13表达水平显著升高,IL-2、IL-10、TGF-β表达水平显著降低;RA患者PBMC的Bcl6 mRNA水平显著增高,而Blimp-1 mRNA的表达显著降低;RA患者的关节滑膜中观察到Bcl6、CXCL13显著高表达。结论外周血Tfr细胞比例减少可能与RA的发生发展有关。

Objective To investigate the potential mechanism of follicular regulatory T(Tfr)cells in the pathogenesis of rheumatoid arthritis(RA).Methods The percentage of CD4^(+)CXCR5^(+)FOXP3^(+)ICOS^(+)Tfr cells in the peripheral blood of 20 patients with RA and 20 healthy subjects were detected by flow cytometry,and the correlation between the proportion of Tfr cells and the clinical laboratory index of RA was analyzed.The serum levels of interleukin-10(IL-10),IL-12,IL-2,transforming growth factor-β(TGF-β)and C-X-C motif chemokine ligand 13(CXCL13)were measured by ELISA.The mRNA expression of Bcl6 and B lymphocyte induced mature protein 1(Blimp-1)in peripheral blood mononuclear cells(PBMCs)was detected by real-time quantitative PCR.Immunohistochemistry was used to detect the expression of Bcl6 and CXCL13 in synovium of RA patients.Results The percentage of Tfr cells in the RA patients significantly decreased compared with the healthy controls,which was negatively related to the C reactive protein(CRP),rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),disease activity score in 28 joints(DAS28).The serum levels of IL-12 and CXCL13 in the patients with RA went up obviously,while the levels of IL-2,IL-10 and TGF-βwent down remarkably.The Bcl6 mRNA level in PBMCs of the RA patients was significantly raised,while the expression of Blimp-1 mRNA was significantly reduced.Bcl6 and CXCL13 were highly expressed in the synovium of the RA patients.Conclusion The decrease of the proportion of Tfr cells in the peripheral blood may be related to the occurrence and development of RA.