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Archives of Dermatological Research

, Volume 307, Issue 4, pp 333–339 | Cite as

Regulation of immune cells in oral lichen planus

  • F. A. Firth
  • L. T. Friedlander
  • V. P. B. Parachuru
  • T. B. Kardos
  • G J. Seymour
  • A. M. RichEmail author
Original Paper

Abstract

Oral lichen planus (OLP) is an immunological disease and while it is understood that the T cell subsets, FoxP3+ Tregs and IL17+ Th17 cells are involved in immune regulation, little is known about their presence in OLP. The aims of this study were to compare the number of cells expressing FoxP3 or IL-17 in OLP with non-specifically inflamed oral mucosa and to determine which cell types expressed FoxP3 and/or IL-17 and their distribution. Immunohistochemistry was used to investigate the presence of FoxP3+ or IL-17+ cells in 12 control cases and 17 cases of OLP. These results were analysed quantitatively and qualitatively. Double-labelling immunofluorescence (IF) was used to determine the type of cell expressing FoxP3/IL-17 and these results were analysed qualitatively. OLP displayed significantly more FoxP3+ cells (mean 79.3 vs. 20.6 cells/defined area, p < 0.0001) and fewer IL-17+ cells (mean 1.05 vs. 3.30 cells/defined area, p = 0.0003) than non-specific inflammatory cases. The majority of FoxP3+ cells were in the sub-epithelial infiltrate, while IL-17+ cells were deeper in the stromal tissues. IF showed that FoxP3+ cells co-localised with T cells, while the IL-17+ cells did not. These results show that the balance between Tregs and IL-17+ cells is altered in OLP, thus supporting the proposition that disturbance in local immune regulation is important in the pathogenesis of OLP. The observation that the IL-17+ cells were mast cells has not previously been reported in OLP and again raises questions about the role of mast cells in this condition.

Keywords

Oral lichen planus Immune regulation FoxP3 IL-17 

Notes

Acknowledgments

The assistance provided by Ms Lynda Horne, Charge Medical Laboratory Scientist, Medlab Dental is gratefully acknowledged. This research was conducted was FAF was the recipient of an Otago Medical Research Foundation Summer Studentship Scholarship.

References

  1. 1.
    Beriou G, Costantino CM, Ashley CW, Yang L, Kuchroo VK, Baecher-Allan C et al (2009) IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113:4240–4249CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Chen X, O’Shea JJ (2008) Regulation of IL-17 production in human lymphocytes. Cytokine 41:71–78CrossRefPubMedGoogle Scholar
  3. 3.
    Chen X, Oppenheim JJ (2011) Resolving the identity myth: key markers of functional CD47FoxP3+ regulatory T cells. Int Immunopharmacol 11:1489–1496CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Davari P, Hsiao HH, Fazel N (2014) Mucosal oral lichen planus: an evidence—based treatment update. Am J Clin Dermatol 15:181–195CrossRefPubMedGoogle Scholar
  5. 5.
    Di Stasio D, Guida A, Salerno C, Contaldo M, Esposito V, Laino et al (2014) Oral lichen planus: a narrative review. Front Biosci 6:370–376CrossRefGoogle Scholar
  6. 6.
    Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061CrossRefPubMedGoogle Scholar
  7. 7.
    Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J et al (2010) Cutting edge: mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184:3336–3340CrossRefPubMedGoogle Scholar
  8. 8.
    Jontell M, Hansson H-A, Nygren H (1986) Mast cells in oral lichen planus. J Oral Pathol Med 15:273–275CrossRefGoogle Scholar
  9. 9.
    Khan A, Farah CS, Savage NW, Walsh LJ, Harbrow DJ, Sugerman PB (2003) Th1 cytokines in oral lichen planus. J Oral Pathol Med 32:77–83CrossRefPubMedGoogle Scholar
  10. 10.
    Liew F, Pitman N, McInnes I (2010) Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10:103–110CrossRefPubMedGoogle Scholar
  11. 11.
    Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S et al (2011) Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol 187:490–500CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K (2005) Current controversies in oral lichen planus: report of an international consensus meeting. Oral Surg Oral Med Oral Pathol 100:40–51CrossRefGoogle Scholar
  13. 13.
    Lu R, Zeng X, Han Q, Lin M, Long L, Dan H et al (2014) Overexpression and selectively regulatory roles of IL-23/Il-17 axis in the lesions of oral lichen planus. Med Inflamm. doi: 10.1155/2014/701094 Google Scholar
  14. 14.
    O’Connor RACT, Prendergast CA, Sabatos CW (2008) Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis. J. Immunol 181:3750–3754CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Payeras MR, Cherubini K, Figueiredo MA, Salum FG (2013) Oral lichen planus: focus on etiopathogenesis. Arch Oral Biol 100:1057–1069CrossRefGoogle Scholar
  16. 16.
    Pereira JS, Monteiro BV, Nonaka CF, Silveira EJ, Miguel MC (2012) FoxP3(+) T regulatory cells in oral lichen planus and its correlation with the distinct clinical appearance of the lesions. Int J Exp Pathol 93:287–294CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Piccirillo CA, Tritt M, Sgouroudis E, Albanese A, Pyzik M, Hay V (2005) Control of type 1 autoimmune diabetes by naturally occurring CD4 + CD25 + regulatory T lymphocytes in neonatal NOD mice. Ann NY Acad Sci 1051:72–87CrossRefPubMedGoogle Scholar
  18. 18.
    Shen Z, Gao X, Ma L, Zhou Z, Shen X, Liu W (2014) Expression of Foxp3 and interleukin-17 in lichen planus lesions with emphasis on difference in oral and cutaneous variants. Arch Dermatol Res 306:441–446CrossRefPubMedGoogle Scholar
  19. 19.
    Sugerman PB, Savage NW, Walsh LJ, Zhao ZZ, Zhou XJ, Khan A et al (2002) The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med 13:350–365CrossRefPubMedGoogle Scholar
  20. 20.
    Tao XA, Xia J, Chen XB, Wang H, Dai YH, Rhodus NL et al (2010) FoxP3 + T regulatory cells in lesions of oral lichen planus correlated with disease activity. Oral Dis 16:76–82CrossRefPubMedGoogle Scholar
  21. 21.
    Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β: the role of T regulatory cells. Immunol 117:433–442CrossRefGoogle Scholar
  22. 22.
    van der Meij EH, van der Waal I (2003) Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J Oral Pathol Med 32:507–512CrossRefPubMedGoogle Scholar
  23. 23.
    Walsh LJ, Savage NW, Ishii T, Seymour GJ (1990) Immunopathogenesis of oral lichen planus. J Oral Pathol Med 19:389–396CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang l, Yang X-Q, Chen J, Hui R-S, Gao T-W (2010) Increased Th17 cells are accompanied by FoxP3+ Treg cell accumulation and correlated with psoriasis disease severity. Clin Immunol 135:108–117CrossRefPubMedGoogle Scholar
  25. 25.
    Zhou XJ, Sugerman PB, Savage NW, Walsh LJ, Seymour GJ (2002) Intra-epithelial CD8+ T cell and basement membrane disruption in oral lichen planus. J Oral Pathol Med 31:23–27CrossRefPubMedGoogle Scholar
  26. 26.
    Zhu J, Paul WE (2010) Heterogeneity and plasticity of T helper cells. Cell Res 20:4–12CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • F. A. Firth
    • 1
  • L. T. Friedlander
    • 1
  • V. P. B. Parachuru
    • 1
  • T. B. Kardos
    • 1
  • G J. Seymour
    • 1
  • A. M. Rich
    • 1
    Email author
  1. 1.Sir John Walsh Research Institute, Faculty of DentistryUniversity of OtagoDunedinNew Zealand

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