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Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis

  • Nephrology - Original Paper
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Abstract

Background

Tonsillitis can promote the progression of IgA nephropathy (IgAN) by aggravating immunopathologic response. Th22 cell disorder is involved in the pathogenesis of IgAN with tonsillitis. This study was determined to explore the possible mechanism of IgAN with tonsillitis underlying Th22 cell chemotaxis response to the effect of CCL20, CCL22, and CCL27.

Methods

This research was conducted on 65 subjects including 16 healthy controls (HC group), 5 patients with  renal carcinoma (HTC group) and 44 patients with IgAN between 2015 and 2016. According to clinical symptoms and results of throat swab culture, patients with IgAN were divided into two groups: IgAN with tonsillitis (IgAN + tonsillitis, n = 14) and IgAN patients without tonsillitis (IgAN, n = 30). Distribution of Th22 cells in IgAN patients was determined. The expression of CCL20, CCL22, and CCL27 in both peripheral blood and kidneys of IgAN patients was investigated. Severity of pathological lesions in IgAN patients was analyzed. Coculture assay and transwell assay were performed to explore the impacts of human mesangial cells (HMC) on Th22 cell chemotaxis and Th22 cell local accumulation under hemolytic streptococcus (HS) infection.

Results

Th22 cell percentages in IgAN patients increased compared with healthy controls. This increased Th22 cell percentage was positively correlated with the renal lesions of IgAN patients. Correspondingly, the expression of CCL20, CCL22, and CCL27 in renal tissue increased in IgAN patients. Tonsillitis exacerbated these overrepresentations of Th22 cells and chemokines. It was found that HMC could produce CCL20, CCL22, and CCL27. The supernatant of HMC was chemotactic for Th22 cells. This activity of HMC was stimulated by HS infection, whereas treatment of anti-CCL20, anti-CCL22, and anti-CCL27 antibodies partly blocked this chemoattractant effect of HMC.

Conclusions

Tonsil infection may aggravate the renal pathological lesions of IgAN by exacerbating Th22 cell accumulation. Our data suggested a collaboration between HMC and Th22 cells in IgAN with tonsillitis underlying the effects of CCL20, CCL22, and CCL27.

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References

  1. Markowitz G (2017) Glomerular disease: updated oxford classification of IgA nephropathy: a new MEST-C score. Nat Rev Nephrol 13:385–386

    Article  PubMed  CAS  Google Scholar 

  2. Strippoli GF, Maione A, Schena FP et al (2009) IgA nephropathy: a disease in search of a large-scale clinical trial to reliably inform practice. Am J Kidney Dis 53:5–8

    Article  PubMed  Google Scholar 

  3. Floege J, Feehally J (2016) The mucosa-kidney axis in IgA nephropathy. Nat Rev Nephrol 2:147–156

    Article  CAS  Google Scholar 

  4. Huang H, Peng Y, Liu H et al (2010) Decreased CD4+ CD25+ cells and increased dimeric IgA-producing cells in tonsils in IgA nephropathy. J Nephrol 23:202–209

    PubMed  CAS  Google Scholar 

  5. Jia L, Wu C (2014) The bilogy and functions of Th22 cells. Adv Exp Med Biol 841:209–230

    Article  PubMed  CAS  Google Scholar 

  6. Wang B, Komers R, Carew R et al (2012) Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol 23:252–265

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kanapathippillai P, Hedberg A, Fenton CG et al (2013) Nucleosomes contribute to increase mesangial cell chemokine expression during the development of lupus nephritis. Cytokine 62:244–252

    Article  PubMed  CAS  Google Scholar 

  8. Meng T, Li X, Ao X et al (2014) Hemolytic streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20 response to the effect of Th17 cells. PLoS ONE 29:e108723

    Article  CAS  Google Scholar 

  9. Ye Zhi-Jian, Zhou Qiong, Yuan Ming-Li et al (2012) Differentiation and recruitment of IL-22-producing helper T cells stimulated by pleural mesothelial cells in tuberculous pleurisy. Am J Respir Crit Care Med 185:660–669

    Article  PubMed  CAS  Google Scholar 

  10. Trimarchi H, Barratt J, Cattran DC et al (2017) Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int 91:1014–1021

    Article  PubMed  Google Scholar 

  11. Demmers MW, Korevaar SS, Roemeling-van Rhijn M et al (2015) Human renal tubular epithelial cells suppress alloreactive T cell proliferation. Clin Exp Immunol 179:509–519

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Blasi M, Balakumaran B, Chen P et al (2014) Renal epithelial cells produce and spread HIV-1 via T-cell contact. AIDS 28:2345–2353

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Yamamoto Y, Hiki Y, Nakai S et al (2013) Comparison of effective impact among tonsillectomy alone, tonsillectomy combined with oral steroid and with steroid pulse therapy on long-term outcome of immunoglobulin a nephropathy. Clin Exp Nephrol 17:218–224

    Article  PubMed  CAS  Google Scholar 

  14. Korn T, Bettelli E, Oukka M et al (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517

    Article  PubMed  CAS  Google Scholar 

  15. Chen F, Ma YL, Ding H et al (2015) Effects of Tripterygium wilfordii glycosides on regulatory T cells and Th17 in an IgA nephropathy rat model. Genet Mol Res 14:14900–14907

    Article  PubMed  CAS  Google Scholar 

  16. Zhang X, Wu X, Xiong L et al (2014) Role of vitamin D3 in regulation of T helper cell 17 and regulatory T-cell balance in rats with immunoglobulin a nephropathy. Iran J Kidney Dis 8:363–370

    PubMed  Google Scholar 

  17. Lin FJ, Jiang GR, Shan JP et al (2012) Imbalance of regulatory T cells to Th17 cells in IgA nephropathy. Scand J Clin Lab Invest 72:221–229

    Article  PubMed  CAS  Google Scholar 

  18. Yang L, Zhang X, Peng W et al (2017) MicroRNA-155-induced T lymphocyte subgroup drifting in IgA nephropathy. Int Urol Nephrol 49:353–361

    Article  PubMed  CAS  Google Scholar 

  19. Stangou M, Bantis C, Skoularopoulou M et al (2016) Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis. Indian J Nephrol 26:159–166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Peng Z, Tian J, Cui X et al (2013) Increased number of Th22 cells and correlation with Th17 cells in peripheral blood of patients with IgA nephropathy. Hum Immunol 74:1586–1591

    Article  PubMed  CAS  Google Scholar 

  21. Suh JS, Cho SH, Chung JH et al (2013) A polymorphism of interleukin-22 receptor alpha-1 is associated with the development of childhood IgA nephropathy. J Interferon Cytokine Res 33:571–577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Weber GF, Schlautkotter S, Kaiser-Moore S et al (2007) Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. Infect Immun 75:1690–1697

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Ridiandries A, Tan JT, Bursill CA (2016) The role of CC-Chemokines in the regulation of angiogenesis. Int J Mol Sci 17:E1856

    Article  PubMed  CAS  Google Scholar 

  24. Paust HJ, Turner JE, Riedel JH et al (2012) Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis. Kidney Int 82:72–83

    Article  PubMed  CAS  Google Scholar 

  25. Turner JE, Paust HJ, Steinmetz OM et al (2010) CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis. J Am Soc Nephrol 21:974–985

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Xiao C, Zhou Q, Li X et al (2017) Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy. Int Immunopharmacol 42:203–208

    Article  PubMed  CAS  Google Scholar 

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Funding

This work was supported by grants from the National Natural Science Foundation of China (nos. 81470933 and 81270786) (http://www.nsfc.gov.cn/).

Author information

Author notes

  1. Lu Gan, Mengyuan Zhu: these authors contributed equally to this work.

  2. Xiaozhao Li, Ting Meng, Jiaxi Pu, Qiaoling Zhou: these authors contributed equally to this work.

  3. Huiming Luo, Fengmin Shao: these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, First People’s Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, Yunnan, China

    Lu Gan & Huiming Luo

  2. Department of Nephrology, People’s Hospital of Zhengzhou University, Henan, China

    Mengyuan Zhu & Fengmin Shao

  3. Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xiaozhao Li, Chen Chen, Ting Meng, Jiaxi Pu & Qiaoling Zhou

Authors
  1. Lu Gan
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  2. Mengyuan Zhu
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  3. Xiaozhao Li
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  4. Chen Chen
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  5. Ting Meng
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  6. Jiaxi Pu
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  7. Huiming Luo
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  8. Fengmin Shao
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  9. Qiaoling Zhou
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Corresponding author

Correspondence to Qiaoling Zhou.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All patients were recruited and examined in the Xiangya Hospital, Central South University. This study was carried out according to the Declaration of Helsinki and approved by the Medical Ethics Committee of the Xiangya Hospital of Central South University for Human Studies (approval number 201403270).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Cite this article

Gan, L., Zhu, M., Li, X. et al. Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis. Int Urol Nephrol 50, 1285–1292 (2018). https://doi.org/10.1007/s11255-018-1792-2

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  • DOI: https://doi.org/10.1007/s11255-018-1792-2

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