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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 9086-9094
    |
    Published online on: October 4, 2017
       https://doi.org/10.3892/mmr.2017.7724
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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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1 

Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, et al: Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 363:343–354. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Phoon RK, Kitching AR, Odobasic D, Jones LK, Semple TJ and Holdsworth SR: T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 19:477–485. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Tipping PG and Holdsworth SR: T cells in crescentic glomerulonephritis. J Am Soc Nephrol. 17:1253–1263. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Zhang Q, Luan H, Wang L, He F, Zhou H, Xu X, Li X, Xu Q, Niki T, Hirashima M, et al: Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice. Am J Physiol Renal Physiol. 306:F822–F832. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Hünemörder S, Treder J, Ahrens S, Schumacher V, Paust HJ, Menter T, Matthys P, Kamradt T, Meyer-Schwesinger C, Panzer U, et al: TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis. J Pathol. 237:62–71. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Mosmann TR, Cherwinski H, Bond MW, Giedlin MA and Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 136:2348–2357. 1986.PubMed/NCBI

7 

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM and Weaver CT: Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 6:1123–1132. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Sakaguchi S, Sakaguchi N, Asano M, Itoh M and Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 155:1151–1164. 1995.PubMed/NCBI

9 

Kitching AR and Holdsworth SR: The emergence of TH17 cells as effectors of renal injury. J Am Soc Nephrol. 22:235–238. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Fehérvari Z and Sakaguchi S: CD4+ Tregs and immune control. J Clin Invest. 114:1209–1217. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Barbi J, Pardoll D and Pan F: Metabolic control of the Treg/Th17 axis. Immunol Rev. 252:52–77. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Campbell DJ and Koch MA: Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat Rev Immunol. 11:119–130. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, et al: Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 29:44–56. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Zhu J, Yamane H and Paul WE: Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 28:445–489. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Lee YK, Mukasa R, Hatton RD and Weaver CT: Developmental plasticity of Th17 and treg cells. Curr Opin Immunol. 21:274–280. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Norton JD: ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci. 113:3897–3905. 2000.PubMed/NCBI

17 

Nakatsukasa H, Zhang D, Maruyama T, Chen H, Cui K, Ishikawa M, Deng L, Zanvit P, Tu E, Jin W, et al: The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells. Nat Immunol. 16:1077–1084. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Bain G, Cravatt CB, Loomans C, Alberola-lla J, Hedrick SM and Murre C: Regulation of the helix-loop-helix proteins, E2A and ID3, by the Ras-ERK MAPK cascade. Nat Immunol. 2:165–171. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Pan L, Sato S, Frederick JP, Sun XH and Zhuang Y: Impaired immune responses and B-cell proliferation in mice lacking the ID3 gene. Mol Cell Biol. 19:5969–5980. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Murre C: Helix-loop-helix proteins and lymphocyte development. Nat Immunol. 6:1079–1086. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Maruyama T, Li J, Vaque JP, Konkel JE, Wang W, Zhang B, Zhang P, Zamarron BF, Yu D, Wu Y, et al: Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor ID3. Nat Immunol. 12:86–95. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Miyazaki M, Miyazaki K, Chen S, Itoi M, Miller M, Lu LF, Varki N, Chang AN, Broide DH and Murre C: Id2 and ID3 maintain the regulatory T cell pool to suppress inflammatory disease. Nat Immunol. 15:767–776. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Kee BL, Quong MW and Murre C: E2A proteins: Essential regulators at multiple stages of B-cell development. Immunol Rev. 175:138–149. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Jones ME and Zhuang Y: Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors. Immunity. 27:860–870. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Le Hir M: Histopathology of humorally mediated anti-glomerular basement membrane (GBM) glomerulonephritis in mice. Nephrol Dial Transplant. 19:1875–1880. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Abbas AK, Murphy KM and Sher A: Functional diversity of helper T lymphocytes. Nature. 383:787–793. 1996. View Article : Google Scholar : PubMed/NCBI

28 

Tipping PG, Huang XR, Qi M, Van GY and Tang WW: Crescentic glomerulonephritis in CD4- and CD8-deficient mice. Requirement for CD4 but not CD8 cells. Am J Pathol. 152:1541–1548. 1998.PubMed/NCBI

29 

Huang XR, Tipping PG, Shuo L and Holdsworth SR: Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice. Kidney Int. 51:94–103. 1997. View Article : Google Scholar : PubMed/NCBI

30 

Robertson J, Wu J, Arends J, Zhou C, Adrogue HE, Chan JT and Lou Y: Spontaneous recovery from early glomerular inflammation is associated with resistance to anti-GBM glomerulonephritis: Tolerance and autoimmune tissue injury. J Autoimmun. 30:246–256. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Rivera RR, Johns CP, Quan J, Johnson RS and Murre C: Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, ID3. Immunity. 12:17–26. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Zhang F, Fuss IJ, Yang Z and Strober W: Transcription of RORγt in developing Th17 cells is regulated by E-proteins. Mucosal Immunol. 7:521–532. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhou H, Wang L, Xu Q, Liu Q, Liu H, Qiu W, Hu T, Lv Y and Zhang Q: ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells. Mol Med Rep 16: 9086-9094, 2017.
APA
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W. ... Zhang, Q. (2017). ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells. Molecular Medicine Reports, 16, 9086-9094. https://doi.org/10.3892/mmr.2017.7724
MLA
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W., Hu, T., Lv, Y., Zhang, Q."ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells". Molecular Medicine Reports 16.6 (2017): 9086-9094.
Chicago
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W., Hu, T., Lv, Y., Zhang, Q."ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells". Molecular Medicine Reports 16, no. 6 (2017): 9086-9094. https://doi.org/10.3892/mmr.2017.7724
Copy and paste a formatted citation
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Spandidos Publications style
Zhou H, Wang L, Xu Q, Liu Q, Liu H, Qiu W, Hu T, Lv Y and Zhang Q: ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells. Mol Med Rep 16: 9086-9094, 2017.
APA
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W. ... Zhang, Q. (2017). ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells. Molecular Medicine Reports, 16, 9086-9094. https://doi.org/10.3892/mmr.2017.7724
MLA
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W., Hu, T., Lv, Y., Zhang, Q."ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells". Molecular Medicine Reports 16.6 (2017): 9086-9094.
Chicago
Zhou, H., Wang, L., Xu, Q., Liu, Q., Liu, H., Qiu, W., Hu, T., Lv, Y., Zhang, Q."ID3 may protect mice from anti‑GBM glomerulonephritis by regulating the differentiation of Th17 and Treg cells". Molecular Medicine Reports 16, no. 6 (2017): 9086-9094. https://doi.org/10.3892/mmr.2017.7724
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