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Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Kidney Injury | Research

Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire

Authors: Chao Zhu, Qing Liang, Yaqun Liu, Deliang Kong, Jie Zhang, Hu Wang, Kejia Wang, Zhiyong Guo

Published in: Journal of Translational Medicine | Issue 1/2019

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Abstract

Background

Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. However, the role of γδT cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal γδT cells and T cell receptor δ (TCRδ) immune repertoires in response to interactions with CaOx crystals.

Methods

CaOx crystal mouse model was established by glyoxylate injection. Flow cytometer was used to analyze the expression of CD69 and IL-17 from intrarenal γδT cells. Furthermore, TCR immune repertoire sequencing (IR-Seq) was used to monitor the profile of the TCRδ immune repertoire.

Results

Our results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal γδT cells. In TCRδ immune repertoire, the majority of V/J gene and V–J/V–D–J combination segments, barring individual exceptions, were similar between kidneys with CaOx formation and control kidneys. Impressively, high complementarity determining region 3 (CDR3) diversity was observed in response to CaOx crystal formation along with distinct CDR3 distribution and abundance.

Conclusion

Our work suggests the presence of aberrant γδT cell activation and reconstitution of the TCRδ immune repertoire in response to CaOx crystal deposition.
Appendix
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Literature
1.
go back to reference Alelign T, Petros B. Kidney stone disease: an update on current concepts. Adv Urol. 2018;2018:3068365.CrossRef Alelign T, Petros B. Kidney stone disease: an update on current concepts. Adv Urol. 2018;2018:3068365.CrossRef
2.
go back to reference Zeng G, Mai Z, Xia S, Wang Z, Zhang K, Wang L, Long Y, Ma J, Li Y, Wan SP, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int. 2017;120:109–16.CrossRef Zeng G, Mai Z, Xia S, Wang Z, Zhang K, Wang L, Long Y, Ma J, Li Y, Wan SP, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int. 2017;120:109–16.CrossRef
3.
go back to reference Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, Novarini A. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346:77–84.CrossRef Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, Novarini A. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346:77–84.CrossRef
4.
go back to reference Ferraro PM, Taylor EN, Eisner BH, Gambaro G, Rimm EB, Mukamal KJ, Curhan GC. History of kidney stones and the risk of coronary heart disease. JAMA. 2013;310:408–15.CrossRef Ferraro PM, Taylor EN, Eisner BH, Gambaro G, Rimm EB, Mukamal KJ, Curhan GC. History of kidney stones and the risk of coronary heart disease. JAMA. 2013;310:408–15.CrossRef
5.
go back to reference Cheungpasitporn W, Thongprayoon C, O’Corragain OA, Edmonds PJ, Ungprasert P, Kittanamongkolchai W, Erickson SB. The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis. QJM. 2015;108:205–12.CrossRef Cheungpasitporn W, Thongprayoon C, O’Corragain OA, Edmonds PJ, Ungprasert P, Kittanamongkolchai W, Erickson SB. The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis. QJM. 2015;108:205–12.CrossRef
6.
go back to reference Jeong IG, Kang T, Bang JK, Park J, Kim W, Hwang SS, Kim HK, Park HK. Association between metabolic syndrome and the presence of kidney stones in a screened population. Am J Kidney Dis. 2011;58:383–8.CrossRef Jeong IG, Kang T, Bang JK, Park J, Kim W, Hwang SS, Kim HK, Park HK. Association between metabolic syndrome and the presence of kidney stones in a screened population. Am J Kidney Dis. 2011;58:383–8.CrossRef
7.
go back to reference Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, Palsson R. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28:1923–42.CrossRef Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, Palsson R. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28:1923–42.CrossRef
8.
go back to reference Vantourout P, Hayday A. Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol. 2013;13:88–100.CrossRef Vantourout P, Hayday A. Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol. 2013;13:88–100.CrossRef
9.
go back to reference Zou C, Zhao P, Xiao Z, Han X, Fu F, Fu L. Gammadelta T cells in cancer immunotherapy. Oncotarget. 2017;8:8900–9.PubMed Zou C, Zhao P, Xiao Z, Han X, Fu F, Fu L. Gammadelta T cells in cancer immunotherapy. Oncotarget. 2017;8:8900–9.PubMed
10.
go back to reference Fleming C, Morrissey S, Cai Y, Yan J. Gammadelta T cells: unexpected regulators of cancer development and progression. Trends Cancer. 2017;3:561–70.CrossRef Fleming C, Morrissey S, Cai Y, Yan J. Gammadelta T cells: unexpected regulators of cancer development and progression. Trends Cancer. 2017;3:561–70.CrossRef
11.
go back to reference Born WK, Kemal Aydintug M, O’Brien RL. Diversity of gammadelta T-cell antigens. Cell Mol Immunol. 2013;10:13–20.CrossRef Born WK, Kemal Aydintug M, O’Brien RL. Diversity of gammadelta T-cell antigens. Cell Mol Immunol. 2013;10:13–20.CrossRef
12.
go back to reference Minculescu L, Sengelov H. The role of gamma delta T cells in haematopoietic stem cell transplantation. Scand J Immunol. 2015;81:459–68.CrossRef Minculescu L, Sengelov H. The role of gamma delta T cells in haematopoietic stem cell transplantation. Scand J Immunol. 2015;81:459–68.CrossRef
13.
go back to reference Kinsey GR, Okusa MD. Expanding role of T cells in acute kidney injury. Curr Opin Nephrol Hypertens. 2014;23:9–16.CrossRef Kinsey GR, Okusa MD. Expanding role of T cells in acute kidney injury. Curr Opin Nephrol Hypertens. 2014;23:9–16.CrossRef
14.
go back to reference Khan SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol. 2013;189:803–11.CrossRef Khan SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol. 2013;189:803–11.CrossRef
15.
go back to reference de Water R, Leenen PJ, Noordermeer C, Nigg AL, Houtsmuller AB, Kok DJ, Schroder FH. Cytokine production induced by binding and processing of calcium oxalate crystals in cultured macrophages. Am J Kidney Dis. 2001;38:331–8.CrossRef de Water R, Leenen PJ, Noordermeer C, Nigg AL, Houtsmuller AB, Kok DJ, Schroder FH. Cytokine production induced by binding and processing of calcium oxalate crystals in cultured macrophages. Am J Kidney Dis. 2001;38:331–8.CrossRef
16.
go back to reference Nazimek K, Filipczak-Bryniarska I, Bryniarski K. The role of medicaments, exosomes and miRNA molecules in modulation of macrophage immune activity. Postepy Hig Med Dosw (Online). 2015;69:1114–29. Nazimek K, Filipczak-Bryniarska I, Bryniarski K. The role of medicaments, exosomes and miRNA molecules in modulation of macrophage immune activity. Postepy Hig Med Dosw (Online). 2015;69:1114–29.
17.
go back to reference Tamura M, Aizawa R, Hori M, Ozaki H. Progressive renal dysfunction and macrophage infiltration in interstitial fibrosis in an adenine-induced tubulointerstitial nephritis mouse model. Histochem Cell Biol. 2009;131:483–90.CrossRef Tamura M, Aizawa R, Hori M, Ozaki H. Progressive renal dysfunction and macrophage infiltration in interstitial fibrosis in an adenine-induced tubulointerstitial nephritis mouse model. Histochem Cell Biol. 2009;131:483–90.CrossRef
18.
go back to reference Li D, Hu L, Liang Q, Zhang C, Shi Y, Wang B, Wang K. Peripheral T cell receptor beta immune repertoire is promptly reconstituted after acute myocardial infarction. J Transl Med. 2019;17:40.CrossRef Li D, Hu L, Liang Q, Zhang C, Shi Y, Wang B, Wang K. Peripheral T cell receptor beta immune repertoire is promptly reconstituted after acute myocardial infarction. J Transl Med. 2019;17:40.CrossRef
19.
go back to reference Liang Q, Liu Z, Zhu C, Wang B, Liu X, Yang Y, Lv X, Mu H, Wang K. Intrahepatic T-cell receptor beta immune repertoire is essential for liver regeneration. Hepatology. 2018;68:1977–90.CrossRef Liang Q, Liu Z, Zhu C, Wang B, Liu X, Yang Y, Lv X, Mu H, Wang K. Intrahepatic T-cell receptor beta immune repertoire is essential for liver regeneration. Hepatology. 2018;68:1977–90.CrossRef
20.
go back to reference Okada A, Nomura S, Higashibata Y, Hirose M, Gao B, Yoshimura M, Itoh Y, Yasui T, Tozawa K, Kohri K. Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection. Urol Res. 2007;35:89–99.CrossRef Okada A, Nomura S, Higashibata Y, Hirose M, Gao B, Yoshimura M, Itoh Y, Yasui T, Tozawa K, Kohri K. Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection. Urol Res. 2007;35:89–99.CrossRef
22.
go back to reference Rosenkranz AR, Knight S, Sethi S, Alexander SI, Cotran RS, Mayadas TN. Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis. Kidney Int. 2000;58:1055–66.CrossRef Rosenkranz AR, Knight S, Sethi S, Alexander SI, Cotran RS, Mayadas TN. Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis. Kidney Int. 2000;58:1055–66.CrossRef
23.
go back to reference Savransky V, Molls RR, Burne-Taney M, Chien CC, Racusen L, Rabb H. Role of the T-cell receptor in kidney ischemia-reperfusion injury. Kidney Int. 2006;69:233–8.CrossRef Savransky V, Molls RR, Burne-Taney M, Chien CC, Racusen L, Rabb H. Role of the T-cell receptor in kidney ischemia-reperfusion injury. Kidney Int. 2006;69:233–8.CrossRef
24.
go back to reference Peng X, Xiao Z, Zhang J, Li Y, Dong Y, Du J. IL-17A produced by both gammadelta T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction. J Pathol. 2015;235:79–89.CrossRef Peng X, Xiao Z, Zhang J, Li Y, Dong Y, Du J. IL-17A produced by both gammadelta T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction. J Pathol. 2015;235:79–89.CrossRef
25.
go back to reference Kurts C, Heymann F, Lukacs-Kornek V, Boor P, Floege J. Role of T cells and dendritic cells in glomerular immunopathology. Semin Immunopathol. 2007;29:317–35.CrossRef Kurts C, Heymann F, Lukacs-Kornek V, Boor P, Floege J. Role of T cells and dendritic cells in glomerular immunopathology. Semin Immunopathol. 2007;29:317–35.CrossRef
26.
go back to reference Chan AJ, Alikhan MA, Odobasic D, Gan PY, Khouri MB, Steinmetz OM, Mansell AS, Kitching AR, Holdsworth SR, Summers SA. Innate IL-17A-producing leukocytes promote acute kidney injury via inflammasome and Toll-like receptor activation. Am J Pathol. 2014;184:1411–8.CrossRef Chan AJ, Alikhan MA, Odobasic D, Gan PY, Khouri MB, Steinmetz OM, Mansell AS, Kitching AR, Holdsworth SR, Summers SA. Innate IL-17A-producing leukocytes promote acute kidney injury via inflammasome and Toll-like receptor activation. Am J Pathol. 2014;184:1411–8.CrossRef
27.
go back to reference Turner JE, Krebs C, Tittel AP, Paust HJ, Meyer-Schwesinger C, Bennstein SB, Steinmetz OM, Prinz I, Magnus T, Korn T, et al. IL-17A production by renal gammadelta T cells promotes kidney injury in crescentic GN. J Am Soc Nephrol. 2012;23:1486–95.CrossRef Turner JE, Krebs C, Tittel AP, Paust HJ, Meyer-Schwesinger C, Bennstein SB, Steinmetz OM, Prinz I, Magnus T, Korn T, et al. IL-17A production by renal gammadelta T cells promotes kidney injury in crescentic GN. J Am Soc Nephrol. 2012;23:1486–95.CrossRef
28.
go back to reference Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988;334:395–402.CrossRef Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988;334:395–402.CrossRef
29.
go back to reference Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human gammadelta T Cells. Science. 2005;309:264–8.CrossRef Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human gammadelta T Cells. Science. 2005;309:264–8.CrossRef
30.
go back to reference Maryanski JL, Casanova JL, Falk K, Gournier H, Jaulin C, Kourilsky P, Lemonnier FA, Luthy R, Rammensee HG, Rotzschke O, et al. The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized. Hum Immunol. 1997;54:117–28.CrossRef Maryanski JL, Casanova JL, Falk K, Gournier H, Jaulin C, Kourilsky P, Lemonnier FA, Luthy R, Rammensee HG, Rotzschke O, et al. The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized. Hum Immunol. 1997;54:117–28.CrossRef
31.
go back to reference Attaf M, Huseby E, Sewell AK. alphabeta T cell receptors as predictors of health and disease. Cell Mol Immunol. 2015;12:391–9.CrossRef Attaf M, Huseby E, Sewell AK. alphabeta T cell receptors as predictors of health and disease. Cell Mol Immunol. 2015;12:391–9.CrossRef
32.
go back to reference Boudinot P, Marriotti-Ferrandiz ME, Pasquier LD, Benmansour A, Cazenave PA, Six A. New perspectives for large-scale repertoire analysis of immune receptors. Mol Immunol. 2008;45:2437–45.CrossRef Boudinot P, Marriotti-Ferrandiz ME, Pasquier LD, Benmansour A, Cazenave PA, Six A. New perspectives for large-scale repertoire analysis of immune receptors. Mol Immunol. 2008;45:2437–45.CrossRef
34.
go back to reference Kalyan S, Kabelitz D. Defining the nature of human gammadelta T cells: a biographical sketch of the highly empathetic. Cell Mol Immunol. 2013;10:21–9.CrossRef Kalyan S, Kabelitz D. Defining the nature of human gammadelta T cells: a biographical sketch of the highly empathetic. Cell Mol Immunol. 2013;10:21–9.CrossRef
Metadata
Title
Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire
Authors
Chao Zhu
Qing Liang
Yaqun Liu
Deliang Kong
Jie Zhang
Hu Wang
Kejia Wang
Zhiyong Guo
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Kidney Injury
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-2022-0

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