ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells

Zhou,Huan; Wang,Le; Xu,Qing; Liu,Qingquan; Liu,Hui; Qiu,Wenhui; Hu,Tingyang; Lv,Yongman; Zhang,Qian

doi:10.3892/mmr.2017.7724

ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells

Authors:
- Huan Zhou
- Le Wang
- Qing Xu
- Qingquan Liu
- Hui Liu
- Wenhui Qiu
- Tingyang Hu
- Yongman Lv
- Qian Zhang
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Affiliations: Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: October 4, 2017 https://doi.org/10.3892/mmr.2017.7724
Pages: 9086-9094

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Abstract

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.

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