Department of Nephrology, Shanghai Jiao Tong University, Shanghai, China.
Scand J Clin Lab Invest. 2012 May;72(3):221-9. doi: 10.3109/00365513.2011.652158. Epub 2012 Jan 25.
Dysregulation of CD4 (+) T cell subsets participates in the pathogenesis of IgA nephropathy (IgAN). FoxP3 (+) regulatory T cells (Treg) and Th17 cells are two novel subsets of CD4 (+) T cells. This study aims to investigate Treg/Th17 balance in IgAN patients.
Peripheral frequencies of Th17 and Treg functional subsets - CD45RA (+) FoxP3(low) resting Treg (rTreg) and CD45RA(-)FoxP3(high) activated Treg (aTreg) were assessed in 63 adult IgAN patients. Expression of transcription factors (FoxP3 and RORγt) and related cytokines of Treg and Th17 were analysed. Renal expression of FoxP3 and IL-17A were detected by immunohistochemistry.
Compared with normal controls, IgAN patients had decreased frequency of CD45RA(-)FoxP3(high) aTreg subset (p < 0.05), increased frequency of Th17 (p < 0.05) and decreased ratio of Treg/Th17 (p < 0.05). Frequency of aTreg subset correlated with SBP(r = - 0.57, p < 0.05), DBP (r = - 0.50, p < 0.05), eGFR (r = 0.68, p < 0.05) and 24 h proteinuria (r = - 0.58, p < 0.05). RORγtmRNA/FoxP3mRNA ratio increased in IgAN (p < 0.05). Serum IL-17A, IL-21, IL-23, IL-1β and IL-6 elevated while IL-10 decreased in IgAN (p < 0.05), and serum IL-17A correlated with 24 h proteinuria (r = 0.35, p < 0.05). Serum TGF-β1 wasn't different between the two groups. Renal interstitial infiltration of FoxP3 (+) mononuclear cells were observed in IgAN patients, particularly prominent in those with > 25% tubular atrophy/interstitial fibrosis. Tubular IL-17A expression was found in 34 out of 63 IgAN patients. Compared with 29 patients without IL-17A expression, these patients had lower renal function, greater proteinuria, and more severe tubulointerstitial damage.
Imbalance of Treg/Th17 found in IgAN may play a role in disease pathogenesis and progression.
CD4(+)T 细胞亚群的失调参与了 IgA 肾病（IgAN）的发病机制。FoxP3(+)调节性 T 细胞（Treg）和 Th17 细胞是 CD4(+)T 细胞的两个新亚群。本研究旨在探讨 IgAN 患者中 Treg/Th17 平衡。
评估了 63 例成人 IgAN 患者外周血 Th17 和 Treg 功能亚群 - CD45RA(+)FoxP3(low)静息 Treg（rTreg）和 CD45RA(-)FoxP3(high)激活 Treg（aTreg）的频率。分析了 Treg 和 Th17 的转录因子（FoxP3 和 RORγt）和相关细胞因子的表达。通过免疫组化检测肾组织中 FoxP3 和 IL-17A 的表达。
与正常对照组相比，IgAN 患者 CD45RA(-)FoxP3(high)aTreg 亚群频率降低（p<0.05），Th17 频率升高（p<0.05），Treg/Th17 比值降低（p<0.05）。aTreg 亚群频率与 SBP（r=-0.57，p<0.05）、DBP（r=-0.50，p<0.05）、eGFR（r=0.68，p<0.05）和 24 小时蛋白尿（r=-0.58，p<0.05）相关。IgAN 中 RORγtmRNA/FoxP3mRNA 比值升高（p<0.05）。IgAN 患者血清 IL-17A、IL-21、IL-23、IL-1β 和 IL-6 升高，IL-10 降低（p<0.05），血清 IL-17A 与 24 小时蛋白尿呈正相关（r=0.35，p<0.05）。两组间血清 TGF-β1 无差异。IgAN 患者肾间质浸润 FoxP3(+)单核细胞，尤其是肾小管萎缩/间质纤维化>25%的患者更为明显。在 63 例 IgAN 患者中，有 34 例患者的肾小管中表达 IL-17A。与 29 例无 IL-17A 表达的患者相比，这些患者的肾功能更差，蛋白尿更多，肾小管间质损伤更严重。
在 IgAN 中发现的 Treg/Th17 失衡可能在疾病发病机制和进展中发挥作用。
