Zhang L, Yan J, Yang B, Zhang G, Wang M, Dong S, Liu W, Yang H, Li Q
Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
Department of Nephroimmunology, Children's Hospital, Chongqing Medical University, Chongqing, China.
Scand J Immunol. 2018 Jan;87(1):36-45. doi: 10.1111/sji.12629. Epub 2017 Dec 7.
This study (1) analysed the percentage of γδ T cells, γδ T cell subsets, Th17 cells and regulatory T cells (Treg cells) and (2) determined the role of IL-23 in primary nephrotic syndrome (PNS) patients with active disease and in remission. Eighty-four patients with PNS and 51 healthy age-matched controls were included in this study. The percentage of γδ T cells, γδ T cell subsets, Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) were analysed by fluorescence-activated cell sorting. PMBCs from PNS patients with active disease were cultured in the presence of IL-23, IL-23 and an IL-23 antagonist, or IL23 and an anti-IL-21 monoclonal antibody (mAb). The percentage of γδ T cells, IL-23R γδ T cells and IL-17 γδ T cells were significantly increased in PNS patients with active disease. There was a positive correlation between the percentage of γδ T cells, IL-23R γδ T cells, IL-17 γδ T cells and the Th17/Treg ratio. IL-23 increased the percentage of γδ T cells and Th17 cells and decreased the percentage of Treg cells in PBMCs isolated from PNS patients with active disease. Anti-IL-21 mAb reduced the percentage of γδ T cells and Th17 cells, but increased the percentage of Treg cells. γδ T cells, IL-17 γδ T cells and IL-23R γδ T cells may be involved in the pathogenesis of paediatric PNS by modulating the balance of Th17/Treg cells. γδ T cells may cause an imbalance in Th17/Treg cells by secreting IL-21 in the presence of IL-23.
本研究(1)分析了γδT细胞、γδT细胞亚群、Th17细胞和调节性T细胞(Treg细胞)的百分比,(2)确定了白细胞介素-23(IL-23)在原发性肾病综合征(PNS)活动期和缓解期患者中的作用。本研究纳入了84例PNS患者和51例年龄匹配的健康对照。通过荧光激活细胞分选分析外周血单个核细胞(PBMC)中γδT细胞、γδT细胞亚群、Th17细胞和Treg细胞的百分比。将活动期PNS患者的PMBC在IL-23、IL-23与IL-23拮抗剂或IL-23与抗IL-21单克隆抗体(mAb)存在的情况下进行培养。活动期PNS患者中γδT细胞、IL-23RγδT细胞和IL-17γδT细胞的百分比显著增加。γδT细胞、IL-23RγδT细胞、IL-17γδT细胞的百分比与Th17/Treg比值之间存在正相关。IL-23增加了活动期PNS患者分离的PBMC中γδT细胞和Th17细胞的百分比,并降低了Treg细胞的百分比。抗IL-21 mAb降低了γδT细胞和Th17细胞的百分比,但增加了Treg细胞的百分比。γδT细胞、IL-17γδT细胞和IL-23RγδT细胞可能通过调节Th17/Treg细胞平衡参与小儿PNS的发病机制。γδT细胞可能在IL-23存在的情况下通过分泌IL-21导致Th17/Treg细胞失衡。