Department of Rheumatology, The First Hospital, Jilin University, Changchun, China.
Clin Exp Immunol. 2014 Jul;177(1):212-8. doi: 10.1111/cei.12330.
T cell and T cell-related cytokine abnormalities are involved in the pathogenesis of systemic lupus erythematosus (SLE). Our previous study showed that the interleukin (IL)-22(+) CD4(+) T cells and IL-22 play an important role in the pathogenesis of SLE. In this study, we aimed to investigate the effects of glucocorticoids (GCs) and immunodepressant agents on IL-22 and IL-22-producing T cell subsets in SLE patients. The frequencies of peripheral blood T helper type 22 (Th22), IL-22(+) Th17, IL-22(+) Th1 and Th17 cells and the concentrations of serum IL-22, IL-17 and interferon (IFN)-γ in SLE patients receiving 4 weeks of treatment with cyclophosphamide (CYC), methylprednisolone and hydroxychloroquine (HCQ) were characterized by flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA). The frequencies of Th22, IL-22(+) Th17 and Th17 cells and the concentrations of IL-22 and IL-17 were reduced in response to the drugs methylprednisolone, cyclophosphamide and hydroxychloroquine for 4 weeks in the majority of SLE patients. However, the percentage of Th1 cells showed no change. No differences in the levels of IL-22 and IL-22(+) CD4(+) T cells were found between non-responders and health controls either before or after therapy. IL-22 levels were correlated positively with Th22 cells in SLE patients after treatment. These results suggest that elevated IL-22 is correlated with IL-22(+) CD4(+) T cells, especially Th22 cells, and may have a co-operative or synergetic function in the immunopathogenesis of SLE. GC, CYC and HCQ treatment may regulate the production of IL-22, possibly by correcting the IL-22(+) CD4(+) T cells polarizations in SLE, thus providing new insights into the mechanism of GC, CYC and HCQ in the treatment of SLE.
T 细胞和 T 细胞相关细胞因子异常参与系统性红斑狼疮(SLE)的发病机制。我们之前的研究表明,白细胞介素(IL)-22(+)CD4(+)T 细胞和 IL-22 在 SLE 的发病机制中起重要作用。在这项研究中,我们旨在研究糖皮质激素(GCs)和免疫抑制剂对 SLE 患者 IL-22 和产生 IL-22 的 T 细胞亚群的影响。通过流式细胞术分析和酶联免疫吸附试验(ELISA)分析,研究了接受环磷酰胺(CYC)、甲基强的松龙和羟氯喹(HCQ)治疗 4 周的 SLE 患者外周血辅助性 T 细胞 22(Th22)、IL-22(+)Th17、IL-22(+)Th1 和 Th17 细胞的频率以及血清 IL-22、IL-17 和干扰素(IFN)-γ的浓度。在大多数 SLE 患者中,用甲基强的松龙、环磷酰胺和羟氯喹治疗 4 周后,Th22、IL-22(+)Th17 和 Th17 细胞的频率以及 IL-22 和 IL-17 的浓度降低。然而,Th1 细胞的百分比没有变化。在治疗前后,无反应者和健康对照组之间的 IL-22 和 IL-22(+)CD4(+)T 细胞水平没有差异。SLE 患者治疗后 IL-22 水平与 Th22 细胞呈正相关。这些结果表明,升高的 IL-22 与 IL-22(+)CD4(+)T 细胞,尤其是 Th22 细胞相关,可能在 SLE 的免疫发病机制中具有协同或协同作用。GC、CYC 和 HCQ 治疗可能通过纠正 SLE 中 IL-22(+)CD4(+)T 细胞的极化来调节 IL-22 的产生,从而为 GC、CYC 和 HCQ 治疗 SLE 的机制提供新的见解。