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The Expression of CXCL10/CXCR3 and Effect of the Axis on the Function of T Lymphocyte Involved in Oral Lichen Planus

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Abstract

The etiology of oral lichen planus (OLP) is still not clear. The purpose of this study was to explore the role of CXC chemokine receptor 3(CXCR3) and its ligand CXC motif chemokine 10(CXCL10) in the pathogenesis of OLP. We examined the expression of CXCR3 and CXCL10 in OLP patients and healthy controls by quantitative real-time PCR, Western blotting, ELISAs, and immunohistochemistry, respectively. Moreover, we detected the effects of CXCL10/CXCR3 axis on T lymphocyte migration, proliferation and apoptosis by Transwell assays, CCK8 assays, and flow cytometry. We found that the expression of CXCR3 and CXCL10 was significantly increased in OLP patients. In addition, T lymphocyte migration rate of CXCL10 stimulation group was significantly higher than that of control and CXCR3 antagonist groups. After antagonizing CXCR3, the migration ability of T lymphocytes was significantly decreased, and regardless of whether CXCL10 was added in the upper chamber culture medium, the number of migrating cells was similar. The addition of CXCL10 stimulant could stimulate the proliferation of T lymphocytes, but there was no significant difference compared with control group. After antagonizing CXCR3, the proliferation rate of T lymphocytes was significantly reduced. However, there were no significant differences in the apoptosis rates of T lymphocytes between CXCL10 stimulation group, antagonist CXCR3 group, and control group. Due to the change of expression in CXCR3 and CXCL10, and its interaction in mediating the directional migration of peripheral blood T lymphocytes, affecting the proliferation of T lymphocytes, it suggests that CXCL10/CXCR3 axis may be related to the immune mechanism of OLP.

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References

  1. McCartan, B.E., and C.M. Healy. 2008. The reported prevalence of oral lichen planus: A review and critique. Journal of Oral Pathology & Medicine 37 (8): 447–453.

    Article  CAS  Google Scholar 

  2. van der Waal, I. 2010. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncology 46 (6): 423–425.

    Article  PubMed  Google Scholar 

  3. Wu, Y., G. Zhou, H. Zeng, C.R. Xiong, M. Lin, and H.M. Zhou. 2010. A randomized double-blind, positive-control trial of topical thalidomide in erosive oral lichen planus. Oral Surgery Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 110 (2): 188–195.

    Article  Google Scholar 

  4. Crincoli, V., M.B. Di Bisceglie, M. Scivetti, A. Lucchese, S. Tecco, and F. Festa. 2011. Oral lichen planus: Update on etiopathogenesis, diagnosis and treatment. Immunopharmacol Immunotoxicol 33 (1): 11–20.

    Article  PubMed  Google Scholar 

  5. Suresh, S.S., K. Chokshi, S. Desai, R. Malu, and A. Chokshi. 2016. Medical management of oral lichen planus: A systematic review. Journal of Clinical and Diagnostic Research 10 (2): ZE10–ZE15.

    CAS  PubMed  Google Scholar 

  6. Wang, Y., J. Zhou, S. Fu, C. Wang, and B. Zhou. 2015. A study of association between oral lichen planus and immune balance of Th1/Th2 cells. Inflammation 38 (5): 1874–1879.

    Article  CAS  PubMed  Google Scholar 

  7. Peng, W.Y., Y. Ye, B.A. Rabinovich, C.W. Liu, Y.Y. Lou, M.Y. Zhang, M. Whittington, Y. Yang, W.W. Overwijk, G. Lizee, and P. Hwu. 2010. Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clinical Cancer Research 16 (22): 5458–5468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Altara, R., M. Manca, R.D. Brandao, A. Zeidan, G.W. Booz, and F.A. Zouein. 2016. Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases. Clinical Science (London, England) 130 (7): 463–478.

    Article  CAS  Google Scholar 

  9. van den Borne, P., P.H. Quax, I.E. Hoefer, and G. Pasterkamp. 2014. The multifaceted functions of CXCL10 in cardiovascular disease. BioMed Research International 2014: 893106.

    PubMed  PubMed Central  Google Scholar 

  10. Van Raemdonck, K., P.E. Van den Steen, S. Liekens, J. Van Damme, and S. Struyf. 2015. CXCR3 ligands in disease and therapy. Cytokine & Growth Factor Reviews 26 (3): 311–327.

    Article  Google Scholar 

  11. Andalib, A., H. Doulabi, M. Najafi, M. Tazhibi, and A. Rezaie. 2011. Expression of chemokine receptors on Th1/Th2 CD4+ lymphocytes in patients with multiple sclerosis. Iranian Journal of Immunology 8 (1): 1–10.

    CAS  PubMed  Google Scholar 

  12. Muller, M., S. Carter, M.J. Hofer, and I.L. Campbell. 2010. Review: The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity—a tale of conflict and conundrum. Neuropathology and Applied Neurobiology 36 (5): 368–387.

    Article  CAS  PubMed  Google Scholar 

  13. Marques, C.P., P. Kapil, D.R. Hinton, C. Hindinger, S.L. Nutt, R.M. Ransohoff, T.W. Phares, S.A. Stohlman, and C.C. Bergmann. 2011. CXCR3-dependent plasma blast migration to the central nervous system during viral encephalomyelitis. Journal of Virology 85 (13): 6136–6147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fallahi, P., S.M. Ferrari, G. Elia, F. Nasini, M. Colaci, D. Giuggioli, R. Vita, S. Benvenga, C. Ferri, and A. Antonelli. 2016. Novel therapies for thyroid autoimmune diseases. Expert Review of Clinical Pharmacology 9 (6): 853–861.

    Article  CAS  PubMed  Google Scholar 

  15. Antonelli, A., S.M. Ferrari, D. Giuggioli, E. Ferrannini, C. Ferri, and P. Fallahi. 2014. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmunity Reviews 13 (3): 272–280.

    Article  CAS  PubMed  Google Scholar 

  16. Antonelli, A., S.M. Ferrari, A. Corrado, E. Ferrannini, and P. Fallahi. 2014. CXCR3, CXCL10 and type 1 diabetes. Cytokine & Growth Factor Reviews 25 (1): 57–65.

    Article  CAS  Google Scholar 

  17. Ferrari, S.M., I. Ruffilli, M. Colaci, A. Antonelli, C. Ferri, and P. Fallahi. 2015. CXCL10 in psoriasis. Advances in Medical Sciences 60 (2): 349–354.

    Article  PubMed  Google Scholar 

  18. van der Meij, E.H., and I. van der Waal. 2003. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. Journal of Oral Pathology & Medicine 32 (9): 507–512.

    Article  Google Scholar 

  19. Ferri, E.P., C.B. Gallo, C.S. Abboud, W.H. Yanaguizawa, A. Horliana, D. Silva, C. Pavani, S.K. Bussadori, F.D. Nunes, R.A. Mesquita-Ferrari, K.P.S. Fernandes, and M.F.S.D. Rodrigues. 2018. Efficacy of photobiomodulation on oral lichen planus: A protocol study for a double-blind, randomised controlled clinical trial. BMJ Open 8 (10): e024083.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hu, J.Y., J. Zhang, J.L. Cui, X.Y. Liang, R. Lu, G.F. Du, X.Y. Xu, and G. Zhou. 2013. Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus. Cytokine 62 (1): 141–145.

    Article  CAS  PubMed  Google Scholar 

  21. Liu, L.K., X.Y. Jiang, X.X. Zhou, D.M. Wang, X.L. Song, and H.B. Jiang. 2010. Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: Correlation with the clinicopathological features and patient outcome. Modern Pathology 23 (2): 213–224.

    Article  PubMed  Google Scholar 

  22. Chaiyarit, P., K. Luengtrakoon, W. Wannakasemsuk, V. Vichitrananda, P. Klanrit, D. Hormdee, and R. Noisombut. 2017. Biological functions of melatonin in relation to pathogenesis of oral lichen planus. Medical Hypotheses 104: 40–44.

    Article  CAS  PubMed  Google Scholar 

  23. Flier, J., D.M. Boorsma, P.J. van Beek, C. Nieboer, T.J. Stoof, R. Willemze, and C.P. Tensen. 2001. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. The Journal of Pathology 194 (4): 398–405.

    Article  CAS  PubMed  Google Scholar 

  24. Aggarwal, A., S. Agarwal, and R. Misra. 2007. Chemokine and chemokine receptor analysis reveals elevated interferon-inducible protein-10 (IP)-10/CXCL10 levels and increased number of CCR5+ and CXCR3+ CD4 T cells in synovial fluid of patients with enthesitis-related arthritis (ERA). Clinical and Experimental Immunology 148 (3): 515–519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhou, H., J. Wu, T. Wang, X. Zhang, and D. Liu. 2016. CXCL10/CXCR3 axis promotes the invasion of gastric cancer via PI3K/AKT pathway-dependent MMPs production. Biomedicine & Pharmacotherapy 82: 479–488.

    Article  CAS  Google Scholar 

  26. Coppieters, K.T., N. Amirian, P.P. Pagni, C. Baca Jones, A. Wiberg, S. Lasch, E. Hintermann, U. Christen, and M.G. von Herrath. 2013. Functional redundancy of CXCR3/CXCL10 signaling in the recruitment of diabetogenic cytotoxic T lymphocytes to pancreatic islets in a virally induced autoimmune diabetes model. Diabetes 62 (7): 2492–2499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mirones, I., I. de Prada, A.M. Gomez, A. Luque, R. Martin, M.A. Perez-Jimenez, L. Madero, J. Garcia-Castro, and M. Ramirez. 2013. A role for the CXCR3/CXCL10 axis in Rasmussen encephalitis. Pediatric Neurology 49 (6): 451–457 e451.

    Article  PubMed  Google Scholar 

  28. Ruschpler, P., P. Lorenz, W. Eichler, D. Koczan, C. Hanel, R. Scholz, C. Melzer, H.J. Thiesen, and P. Stiehl. 2003. High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis. Arthritis Research & Therapy 5 (5): R241–R252.

    Article  CAS  Google Scholar 

  29. Teleshova, N., M. Pashenkov, Y.M. Huang, M. Soderstrom, P. Kivisakk, V. Kostulas, M. Haglund, and H. Link. 2002. Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal fluid. Journal of Neurology 249 (6): 723–729.

    Article  PubMed  Google Scholar 

  30. Jatczak-Pawlik, I., D. Ksiazek-Winiarek, D. Wojkowska, K. Jozwiak, K. Jastrzebski, M. Pietruczuk, and A. Glabinski. 2016. The impact of multiple sclerosis relapse treatment on migration of effector T cells—preliminary study. Neurologia i Neurochirurgia Polska 50 (3): 155–162.

    Article  PubMed  Google Scholar 

  31. Cruise, M.W., J.R. Lukens, A.P. Nguyen, M.G. Lassen, S.N. Waggoner, and Y.S. Hahn. 2006. Fas ligand is responsible for CXCR3 chemokine induction in CD4+ T cell-dependent liver damage. Journal of Immunology 176 (10): 6235–6244.

    Article  CAS  Google Scholar 

  32. Bondar, C., R.E. Araya, L. Guzman, E.C. Rua, N. Chopita, and F.G. Chirdo. 2014. Role of CXCR3/CXCL10 axis in immune cell recruitment into the small intestine in celiac disease. PLoS One 9 (2): e89068.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Shimada, A., Y. Oikawa, Y. Yamada, Y. Okubo, and S. Narumi. 2009. The role of the CXCL10/CXCR3 system in type 1 diabetes. The Review of Diabetic Studies 6 (2): 81–84.

    Article  PubMed  Google Scholar 

  34. Ha, Y., H. Liu, S. Zhu, P. Yi, W. Liu, J. Nathanson, R. Kayed, B. Loucas, J. Sun, L.J. Frishman, M. Motamedi, and W. Zhang. 2017. Critical role of the CXCL10/C-X-C chemokine receptor 3 axis in promoting leukocyte recruitment and neuronal injury during traumatic optic neuropathy induced by optic nerve crush. The American Journal of Pathology 187 (2): 352–365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. He, J., C. Lian, Y. Fang, J. Wu, J. Weng, X. Ye, and H. Zhou. 2015. Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model. International Journal of Clinical and Experimental Pathology 8 (11): 14542–14548.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Sidahmed, A.M., A.J. Leon, S.E. Bosinger, D. Banner, A. Danesh, M.J. Cameron, and D.J. Kelvin. 2012. CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro. Cytokine 59 (2): 433–441.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81470748).

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Contributions

Conceived and designed the experiments: FY. Performed the experiments: FJ and WC. Analyzed the data: SC, SJ, WX, and LL. Wrote the paper: FJ and WC.

Corresponding author

Correspondence to Yuan Fan.

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All experiments were informed consent by participants and approved by the Ethics Committee of Nanjing Medical University, Nanjing, China. (2014-132)

Conflict of Interest

The authors declare that they have no competing interests.

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Fang, J., Wang, C., Shen, C. et al. The Expression of CXCL10/CXCR3 and Effect of the Axis on the Function of T Lymphocyte Involved in Oral Lichen Planus. Inflammation 42, 799–810 (2019). https://doi.org/10.1007/s10753-018-0934-0

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