Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Mol Med Rep. 2017 Dec;16(6):9086-9094. doi: 10.3892/mmr.2017.7724. Epub 2017 Oct 4.
Anti‑glomerular basement membrane glomerulonephritis (anti‑GBM GN) is an autoimmune disease that leads to severe and rapidly progressive renal injury. Inhibition of DNA‑binding factor 3 (ID3) serves a key role in autoimmune diseases, such as asthma and Sjögren's syndrome, and in experimental allergic encephalitis models. However, the role of ID3 in the progression of anti‑GBM GN remains unknown. In the present study, ID3 mRNA expression increased between 3‑ and 20‑fold in the renal tissues of anti‑GBM GN mice compared with the Control group, with a peak at day 14 post‑induction. In addition, ID3 protein expression was upregulated from day 7 onwards. The expression of ID3 was also examined in the spleen, and was demonstrated to be increased in the spleen of nephritic mice. T helper 17 (Th17) cells and regulatory T (Treg) cells were present throughout the entire period of observation (from day 7 to day 28) in anti‑GBM GN mice, which may vary at different time points, accompanied with the expression of ID3. In vitro, ID3 expression was increased when CD4+ T cells differentiated into Tregs; however, expression was lower in Th17 cells. Following treatment with ID3 small interfering RNA, RAR‑related orphan receptor γt, but not forkhead box P3, expression increased. Furthermore, increased expression of interleukin‑17A was also observed when ID3 was blocked. In addition, ID3 was able to interact with transcription factor E2A. A significant increase in binding between ID3 and E2A was observed in anti‑GBM GN from day 7 onwards, with a peak at day 14 in both renal tissue and spleen. In conclusion, ID3 may be involved in the differentiation of Th17 and Tregs by downregulating Th17 cells, which is probably associated with binding to E2A. The present results suggested that ID3 may offer protection against anti‑GBM GN in mice.
抗肾小球基底膜肾小球肾炎（抗 GBM GN）是一种自身免疫性疾病，可导致严重且进行性加重的肾损伤。DNA 结合因子 3（ID3）的抑制在哮喘和干燥综合征等自身免疫性疾病以及实验性过敏性脑脊髓炎模型中发挥关键作用。然而，ID3 在抗 GBM GN 进展中的作用尚不清楚。在本研究中，与对照组相比，抗 GBM GN 小鼠的肾组织中 ID3 mRNA 表达增加了 3 到 20 倍，诱导后第 14 天达到峰值。此外，ID3 蛋白表达从第 7 天开始上调。在脾中也检查了 ID3 的表达，发现在肾炎小鼠的脾中表达增加。辅助性 T 细胞 17（Th17）细胞和调节性 T（Treg）细胞在整个观察期（从第 7 天到第 28 天）均存在于抗 GBM GN 小鼠中，这些细胞可能会随 ID3 的表达而变化。在体外，当 CD4+T 细胞分化为 Treg 时，ID3 的表达增加；然而，在 Th17 细胞中表达较低。用 ID3 小干扰 RNA 处理后，RAR 相关孤儿受体 γt 而不是叉头框 P3 的表达增加。此外，当阻断 ID3 时，也观察到白细胞介素 17A 的表达增加。此外，ID3 能够与转录因子 E2A 相互作用。从第 7 天开始，在抗 GBM GN 中观察到 ID3 与 E2A 之间的结合显著增加，在肾组织和脾中均在第 14 天达到峰值。总之，ID3 可能通过下调 Th17 细胞参与 Th17 和 Treg 的分化，这可能与与 E2A 的结合有关。本研究结果表明，ID3 可能在小鼠抗 GBM GN 中提供保护。
