Department of Microbiology, Key Laboratory of Medicine and Biotechnology of Qingdao, Qingdao University Medical College, 308 Ningxia Road, 266071 Qingdao, China.
Rheumatol Int. 2012 Apr;32(4):949-58. doi: 10.1007/s00296-010-1771-0. Epub 2011 Jan 18.
To investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells in patients with lupus nephritis (LN), a total of 60 systemic lupus erythematosus patients and 28 healthy controls (HCs) were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum concentrations of interleukin-17 (IL-17) and transforming growth factor-beta 1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated in LN patients a significant decrease in the frequency of CD4+CD25(high) and CD4+CD25+FoxP3+ T cells and a significant increase in the frequency of Th17 cells in peripheral blood, and the ratio of Th17 to Treg cell frequency was significantly increased along with increased SLEDAI scores. LN patients had a lower percentage and expression of FoxP3 in CD4+CD25(high) T cells than SLE patients without nephritis. The concentration of TGF-β1 was found decreased in SLE patients compared with that from healthy controls, though no significant difference was found between LN patients and SLE patients without nephritis. The expression of IL-17 levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls. Based on our results, the significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.
为了研究狼疮肾炎(LN)患者辅助性 T 细胞 17(Th17)和调节性 T(Treg)细胞的变化,共纳入 60 例系统性红斑狼疮患者和 28 例健康对照者(HCs)。采用流式细胞术分析外周血单个核细胞(PBMCs)中 Th17 细胞和 Treg 细胞的频率。采用酶联免疫吸附试验(ELISA)检测血清白细胞介素-17(IL-17)和转化生长因子-β1(TGF-β1)的浓度。结果表明,LN 患者外周血中 CD4+CD25(high)和 CD4+CD25+FoxP3+T 细胞频率显著降低,Th17 细胞频率显著升高,Th17/Treg 细胞频率比值随 SLEDAI 评分升高而显著升高。与无肾炎的 SLE 患者相比,LN 患者 CD4+CD25(high)T 细胞中 FoxP3 的比例和表达均降低。与健康对照者相比,SLE 患者 TGF-β1 浓度降低,而 LN 患者与无肾炎的 SLE 患者之间无显著差异。与无肾炎和健康对照者相比,LN 患者的 IL-17 水平表达显著升高。基于我们的结果,狼疮肾炎中显著升高的 Th17 细胞伴随着 FoxP3+Treg 细胞的减少,提示 Th17/Treg 功能失衡可能参与了 SLE 患者肾损伤的发病机制。