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Inflammatory cells of immunosuppressive phenotypes in oral lichen planus have a proinflammatory pattern of expression and are associated with clinical parameters

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Abstract

Objectives

We sought to investigate the expression of cells with immunosuppressive/protumorigenic phenotypes in oral lichen planus (OLP), such as M2-tumor-associated macrophages (TAM2), myeloid-derived suppressive cells (MDSCs), and regulatory T cells (Tregs) in association with clinical parameters.

Materials and methods

Cases of hyperkeratotic (HK)-OLP (n = 23) and erosive (E)-OLP (n = 26) were immunohistochemically stained to determine the percentages of CD163-TAM2, CD80-MDSCs, and FOXP3-Tregs of proinflammatory CD121a-Th17, CD4 and CD8 lymphocytes, and of cells positive for nuclear factor kappa B (NF-κB) and transforming growth factor beta. Clinical parameters included symptoms, treatment approach, treatment response, and others.

Results

The inflammatory infiltrate in HK-OLP and E-OLP contained immunosuppressive cells; however, their pattern of expression was compatible with a proinflammatory response [membranous CD163-TAM2 staining (not extracellular), CD80+ lymphocytes (not macrophages), and a few Tregs]. The presence of CD4+, CD8+, and CD121a+ T lymphocytes was extensive. TAM2 were more frequent in E-OLP than in HK-OLP (P = 0.017). A higher frequency of CD80+ lymphocytes was associated with partial to no response to treatment (P = 0.028). Nuclear expression of NF-κB in the inflammatory cells was absent.

Conclusions

The pattern of expression of the immunosuppressive cells, together with numerous CD4+, CD8+, and Th17-CD121a+ lymphocytes, suggest an extensive proinflammatory response rather than an immunosuppressive/protumorigenic response.

Clinical relevance

The frequency of selective types of inflammatory cells calls for individual profile analyses of inflammatory infiltrates and individually adjusted treatment.

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References

  1. Roopashree MR, Gondhalekar RV, Shashikanth MC, George J, Thippeswamy SH, Shukla A (2010) Pathogenesis of oral lichen planus—a review. J Oral Pathol Med 39:729–734

    Article  PubMed  Google Scholar 

  2. 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. Part 1. Viral infections and etiopathogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:40–51

    Article  PubMed  Google Scholar 

  3. Zhang J, Zhou G, Du GF, Xu XY, Zhou HM (2011) Biologics, an alternative therapeutic approach for oral lichen planus. J Oral Pathol Med 40:521–524

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. El Naggar AK, Reichart PA (2005) Proliferative verrucous leukoplakia and precancerous condition. In: Barnes L, Eveson JW, Reichart P, Sidransky D (eds) World Organization Classification of tumours. Pathology and genetics. Head and neck tumours. IARC, Lyon, pp 180–181

    Google Scholar 

  6. 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 16:76–82

    Article  PubMed  Google Scholar 

  7. Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117:1155–1166

    Article  PubMed  Google Scholar 

  8. Wang HY, Wang RF (2007) Regulatory T cells and cancer. Curr Opin Immunol 19:217–223

    Article  PubMed  Google Scholar 

  9. Lee YK, Mukasa R, Hatton RD, Weaver CT (2009) Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol 21:274–280

    Article  PubMed  Google Scholar 

  10. Sato M, Tokuda N, Fukumoto T, Mano T, Sato T, Ueyama Y (2006) Immunohistopathological study of the oral lichenoid lesions of chronic GVHD. J Oral Pathol Med 35:33–36

    Article  PubMed  Google Scholar 

  11. Karin M, Greten FR (2005) NF-kappa B: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759

    Article  PubMed  Google Scholar 

  12. Phipps KD, Surette AP, O’Connell PA, Waisman DM (2011) Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites. Cancer Res 71:6676–6683

    Article  PubMed  Google Scholar 

  13. Hallam S, Escorcio-Correia M, Soper R, Schultheiss A, Hagemann T (2009) Activated macrophages in the tumour microenvironment-dancing to the tune of TLR and NF-kappaB. J Pathol 219:143–152

    Article  PubMed  Google Scholar 

  14. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    Article  PubMed  Google Scholar 

  15. Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183

    Article  PubMed  Google Scholar 

  16. Allavena P, Germano G, Marchesi F, Mantovani A (2011) Chemokines in cancer related inflammation. Exp Cell Res 317:664–673

    Article  PubMed  Google Scholar 

  17. Sethi G, Sung B, Aggarwal BB (2008) Nuclear factor-kappaB activation: from bench to bedside. Exp Biol Med (Maywood) 233:21–31

    Article  Google Scholar 

  18. Gannot G, Gannot I, Vered H, Buchner A, Keisari Y (2006) Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma. Br J Cancer 86:1444–1448

    Article  Google Scholar 

  19. Hirshberg A, Amariglio N, Akrish S, Yahalom R, Rosenbaum H, Okon E et al (2006) Traumatic ulcerative granuloma with stromal eosinophilia—a reactive lesion of the oral mucosa. Am J Clin Pathol 126:522–529

    Article  PubMed  Google Scholar 

  20. Rogers HW, Sheehan KC, Brunt LM, Dower SK, Unanue ER, Schreiber RD (1992) Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice. Proc Natl Acad Sci USA 89:1011–1015

    Article  PubMed  Google Scholar 

  21. Massimo H, Ohguro N, Nomura S, Hashida N, Nakai K, Tano Y (2008) Neutrophil chemotaxis and local expression of interleukin-10 in the tolerance of endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 49:5450–5457

    Article  Google Scholar 

  22. Matsumoto Y, Horiike S, Ohshiro M, Yamamoto M, Sasaki N, Tsutsumi T et al (2010) Expression of master regulators of helper T-cell differentiation in peripheral T-cell lymphoma, not otherwise specified, by immunohistochemical analysis. Am J Clin Pathol 133:281–290

    Article  PubMed  Google Scholar 

  23. Lamb RJ, Capocasale RJ, Duffy KE, Sarisky RT, Mbow ML (2007) Identification and characterization of novel bone marrow myeloid DEC205+ Gr-1+ cell subsets that differentially express chemokine and TLRs. J Immunol 178:7833–7839

    PubMed  Google Scholar 

  24. Quaranta MG, Mattioli B, Spadaro F, Straface E, Giordani L, Ramoni C et al (2003) HIV-1 Nef triggers Vav-mediated signaling pathway leading to functional and morphological differentiation of dendritic cells. FASEB 17:2025–2036

    Article  Google Scholar 

  25. Theilig F, Enke AK, Scolari B, Polzin D, Bachmann S, Koesters R (2011) TGF-β tubular deficiency of von Hippel-Lindau attenuates renal disease progression in anti-GBM glomerulonephritis. Am J Pathol 179:2177–2188

    Article  PubMed  Google Scholar 

  26. Kastelan M, Prpić Massari L, Gruber F, Zamolo G, Zauhar G, Coklo M et al (2004) The role of perforin-mediated apoptosis in lichen planus lesions. Arch Dermatol Res 296:226–230

    Article  PubMed  Google Scholar 

  27. Mignogna MD, Fedele S, Lo Russo L, Lo Muzio L, Bucci E (2004) Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence? Oral Oncol 40:120–130

    Article  PubMed  Google Scholar 

  28. Timmermann M, Buck F, Sorg C, Hogger P (2004) Interaction of soluble CD163 with activated T lymphocytes involves its association with non-muscle myosin heavy chain type A. Immunol Cell Biol 82:479–487

    Article  PubMed  Google Scholar 

  29. Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol 12:715–723

    Article  PubMed  Google Scholar 

  30. Fuentes-Duculan J, Suárez-Fariñas M, Zaba LC, Nograles KE, Pierson KC, Mitsui H et al (2010) A subpopulation of CD163-positive macrophages is classically activated in psoriasis. J Invest Dermatol 130:2412–2422

    Article  PubMed  Google Scholar 

  31. Yamazaki T, Akiba H, Koyanagi A, Azuma M, Yagita H, Okumura K (2005) Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-gamma-induced nitric oxide production. J Immunol 175:1586–1592

    PubMed  Google Scholar 

  32. Long M, Park SG, Strickland I, Hayden MS, Ghosh S (2009) Nuclear factor-κB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31:921–931

    Article  PubMed  Google Scholar 

  33. Torihata H, Ishikawa F, Okada Y, Tanaka Y, Uchida T, Suguro T et al (2004) Irradiation up-regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells. Immunology 112:219–227

    Article  PubMed  Google Scholar 

  34. Yang R, Cai Z, Zhang Y, Yutzy WH, Roby KF, Roden RB (2006) CD80 in immune suppression by mouse ovarian carcinoma–associated Gr-1+CD11b+ myeloid cells. Cancer Res 66:6807–6815

    Article  PubMed  Google Scholar 

  35. Valmori D, Raffin C, Raimbaud I, Ayyoub M (2010) Human RORγt+ TH17 cells preferentially differentiate from naive FOXP3+Treg in the presence of lineage-specific polarizing factors. Proc Natl Acad Sci USA 107:19402–19407

    Article  PubMed  Google Scholar 

  36. Liu G, Ma H, Qiu L, Li L, Cao Y, Ma J et al (2011) Phenotypic and functional switch of macrophages induced by regulatory CD4+CD25+ T cells in mice. Immunol Cell Biol 89:130–142

    Article  PubMed  Google Scholar 

  37. 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. Part 2. Clinical management and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:164–178

    Article  PubMed  Google Scholar 

  38. Keenan AV, Ferraiolo D (2011) Insufficient evidence for effectiveness of any treatment for oral lichen planus. Evid Based Dent 12:85–86

    Article  PubMed  Google Scholar 

  39. 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 13:350–365

    Article  PubMed  Google Scholar 

  40. Mani H, Sidhu GS, Kumari R, Gaddipatil JP, Seth P, Maheshwari RK (2002) Curcumin differentially regulates TGF-β1, its receptors and nitric oxide synthase during impaired wound healing. Biofactors 16:29–43

    Article  PubMed  Google Scholar 

  41. Fu S, Kurzrock R (2010) Development of curcumin as an epigenetic agent. Cancer 116:4670–4676

    Article  PubMed  Google Scholar 

  42. Chainani-Wu N, Madden E, Lozada-Nur F, Silverman S (2011) High-dose curcuminoids are efficacious in the reduction in symptoms and signs of oral lichen planus. J Am Acad Dermatol. doi:10.1016/j.jaad.2011.04.022

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Acknowledgments

The authors would like to thank Mrs. Hana Vered for her technical assistance. Ms. Esther Eshkol is thanked for here editorial assistance. The study was supported by the Dave and Sarah Babish fund, School of Dental Medicine, Tel Aviv University.

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Correspondence to Marilena Vered.

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Vered, M., Fürth, E., Shalev, Y. et al. Inflammatory cells of immunosuppressive phenotypes in oral lichen planus have a proinflammatory pattern of expression and are associated with clinical parameters. Clin Oral Invest 17, 1365–1373 (2013). https://doi.org/10.1007/s00784-012-0814-1

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  • DOI: https://doi.org/10.1007/s00784-012-0814-1

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