Tubular expression of Toll-like receptor 9 in lupus and primary membranous nephropathy

##plugins.themes.academic_pro.article.sidebar##

Published Apr 6, 2024
https://doi.org/10.62438/tunismed.v102i4.4273
Download
PDF
Vol. 102 No. 4 (2024): Tunis Med apr 2024

##plugins.themes.academic_pro.article.main##

Nesrine Elloumi
Research laboratory LR18/SP12 auto-immunity, cancer and immunogenetics, immunology department, Habib Bourguiba university hospital, University of Sfax, Tunisia
Raouia Fakhfakh
Research laboratory LR18/SP12 auto-immunity, cancer and immunogenetics, immunology department, Habib Bourguiba university hospital, University of Sfax, Tunisia
Hatem Masmoudi
Research laboratory LR18/SP12 auto-immunity, cancer and immunogenetics, immunology department, Habib Bourguiba university hospital, University of Sfax, Tunisia
Khawla Kammoun
Research laboratory of renal pathology LR19ES11, Nephrology Department, Hedi Chaker Hospital, University of Sfax, Tunisia

Abstract

Introduction: Toll-like- receptors (TLR) control important aspects of innate and adaptive immune responses. Renal cells are among the non-immune cells that express (TLR).  Therefore, their activation might be implicated in renal tubulo-interstitial injury.


Aim: The study aimed to compare TLR9 expression in patients with primary membranous nephropathy (MN) to patients with lupus membranous nephropathy.


Methods: Kidney sections from 10 Lupus nephritis (LN) patients and ten patients with primary MN were analyzed by immunohistochemistry using anti-human TLR9 antibody.


Results: Results showed that TLR9 expression was weak and exclusively tubular in primary MN patients’ biopsies. There was a significant difference between LN patients’ biopsies and primary MN patients’ biopsies. TLR9 expression was more diffused in LN patients’ specimen than in those with primary MN.


Conclusion: This study focuses on molecular level pathogenesis of MN. The data suggest that the receptors TLR9 may play role in tubulointerstitial injury in the pathogenesis of LN but not primary membranous nephropathy.

Keywords:

Membranous nephropathy, Lupus nephritis, TLR9, Kidney biopsies, Tubular expression , Tubulointerstitial injury

##plugins.themes.academic_pro.article.details##

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

  1. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol Pharm Bull. 2005 May;28(5):886–92.
  2. Satoh T, Akira S. Toll-Like Receptor Signaling and Its Inducible Proteins. Microbiol Spectr. 2016 Dec;4(6).
  3. Takeda K, Akira S. Toll-like receptors. Curr Protoc Immunol. 2015 Apr 1;109:14.12.1-14.12.10.
  4. Moresco EMY, LaVine D, Beutler B. Toll-like receptors. Curr Biol CB. 2011 Jul 12;21(13):R488-493.
  5. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002 Jul 11;418(6894):191–5.
  6. Masum MA, Ichii O, Hosny Ali Elewa Y, Nakamura T, Otani Y, Hosotani M, et al. Overexpression of toll-like receptor 9 correlates with podocyte injury in a murine model of autoimmune membranoproliferative glomerulonephritis. Autoimmunity. 2018 Dec;51(8):386–98.
  7. Pawar RD, Ramanjaneyulu A, Kulkarni OP, Lech M, Segerer S, Anders HJ. Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus. J Am Soc Nephrol JASN. 2007 Jun;18(6):1721–31.
  8. Summers SA, Hoi A, Steinmetz OM, O’Sullivan KM, Ooi JD, Odobasic D, et al. TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy. J Autoimmun. 2010 Dec;35(4):291–8.
  9. Devarapu SK, Anders HJ. Toll-like receptors in lupus nephritis. J Biomed Sci. 2018 Apr 12;25:35.
  10. Lorenz G, Lech M, Anders HJ. Toll-like receptor activation in the pathogenesis of lupus nephritis. Clin Immunol Orlando Fla. 2017 Dec;185:86–94.
  11. Elloumi N, Fakhfakh R, Abida O, Ayadi L, Marzouk S, Hachicha H, et al. Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis. Clin Exp Immunol. 2017 Dec;190(3):328–39.
  12. Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521–30.
  13. Safar-Boueri L, Piya A, Beck LH, Ayalon R. Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. Pediatr Nephrol Berl Ger. 2021 Jan;36(1):19–30.
  14. Elloumi N, Fakhfakh R, Ayadi L, Sellami K, Abida O, Ben Jmaa M, et al. The Increased Expression of Toll-Like Receptor 4 in Renal and Skin Lesions in Lupus Erythematosus. J Histochem Cytochem. 2017 Jul;65(7):389–98.
  15. Lee TP, Huang JC, Liu CJ, Chen HJ, Chen YH, Tsai YT, et al. Interactions of surface-expressed TLR-4 and endosomal TLR-9 accelerate lupus progression in anti-dsDNA antibody transgenic mice. Exp Biol Med Maywood NJ. 2014 Jun;239(6):715–23.
  16. Ramachandran R, Sharma V, Rathi M, Yadav AK, Sharma A, Kohli HS, et al. Association between -1486 T>C and +1174 G>A single nucleotide polymorphisms in TLR9 gene and severity of lupus nephritis. Indian J Nephrol. 2012 Mar;22(2):125–9.
  17. Wang CM, Chang SW, Wu YJJ, Lin JC, Ho HH, Chou TC, et al. Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population. Sci Rep. 2014 Jan 21;4:3792.
  18. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis Off J Natl Kidney Found. 1992 Jul;20(1):1–17.
  19. Song K, Liu L, Zhang X, Chen X. An update on genetic susceptibility in lupus nephritis. Clin Immunol Orlando Fla. 2020 Jan;210:108272.
  20. Chen YT, Wei CC, Ng KL, Chen CH, Chan CJ, Chen XX, et al. Toll-like receptor 9 SNPs are susceptible to the development and progression of membranous glomerulonephritis: 27 years follow-up in Taiwan. Ren Fail. 2013;35(10):1370–5.
  21. Papadimitraki ED, Tzardi M, Bertsias G, Sotsiou E, Boumpas DT. Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response. Lupus. 2009 Aug;18(9):831–5.
  22. Benigni A, Caroli C, Longaretti L, Gagliardini E, Zoja C, Galbusera M, et al. Involvement of renal tubular Toll-like receptor 9 in the development of tubulointerstitial injury in systemic lupus. Arthritis Rheum. 2007 May;56(5):1569–78.
  23. Espeli M, Bökers S, Giannico G, Dickinson HA, Bardsley V, Fogo AB, et al. Local renal autoantibody production in lupus nephritis. J Am Soc Nephrol JASN. 2011 Feb;22(2):296–305.
  24. Starke C, Frey S, Wellmann U, Urbonaviciute V, Herrmann M, Amann K, et al. High frequency of autoantibody-secreting cells and long-lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice. Eur J Immunol. 2011 Jul;41(7):2107–12.
  25. Yung S, Chan TM. Anti-dsDNA antibodies and resident renal cells - Their putative roles in pathogenesis of renal lesions in lupus nephritis. Clin Immunol Orlando Fla. 2017 Dec;185:40–50.
  26. Yung S, Chan TM. Molecular and Immunological Basis of Tubulo-Interstitial Injury in Lupus Nephritis: a Comprehensive Review. Clin Rev Allergy Immunol. 2017 Apr;52(2):149–63.
  27. Hong S, Healy H, Kassianos AJ. The Emerging Role of Renal Tubular Epithelial Cells in the Immunological Pathophysiology of Lupus Nephritis. Front Immunol. 2020;11:578952.