The Pathogenesis of Oral Lichen Planus
Tóm tắt
Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8+ cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-β1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft- versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-α, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-β1, TNF-α, IFN-γ, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.
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Tài liệu tham khảo
Allen CM, Camisa C (2000). Paraneoplastic pemphigus: a review of the literature. Oral Dis 6:208–214.
Balasa B, Krahl T, Patstone G, Lee J, Tisch R, McDevitt HO, et al. (1997). CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 159:4620–4627.
Bowen GM, Peters NT, Fivenson DP, Su LD, Nousari HC, Anhalt GJ, et al. (2000). Lichenoid dermatitis in paraneoplastic pemphigus: a pathogenic trigger of epitope spreading? Arch Dermatol 136:652–656.
Bowers KE, Sexton J, Sugerman PB (2000). Commentary. Clin Dermatol 18:497–498.
Chaiyarit P, Kafrawy AH, Miles DA, Zunt SL, Van Dis ML, Gregory RL (1999). Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins (CKs) and a unifying hypothesis of pathogenesis. J Oral Pathol Med 28:210–215.
Dang H, Geiser AG, Letterio JJ, Nakabayashi T, Kong L, Fernandes G, et al. (1995). SLE-like autoantibodies and Sjögren’s syndrome-like lymphoproliferation in TGF-beta knockout mice. J Immunol 155:3205–3212.
Hashimoto K (1976). Apoptosis in lichen planus and several other dermatoses. Acta Dermatol Venereol 56:187–210.
Johns LD, Flanders KC, Ranges GE, Sriram S (1991). Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. J Immunol 147:1792–1796.
Jungell P, Konttinen YT, Malmström M (1989a). Basement membrane changes in oral lichen planus. Proc Finn Dent Soc 85:119–124.
Jungell P, Konttinen YT, Nortamo P, Malmström M (1989b). Immunoelectron microscopic study of distribution of T cell subsets in oral lichen planus. Scand J Dent Res 97:361–367.
Kang K, Kubin M, Cooper KD, Lessin SR, Trinchieri G, Rook AH (1996). IL-12 synthesis by human Langerhans cells. J Immunol 156:1402–1407.
Kaur I, Voss SD, Gupta RS, Schell K, Fisch P, Sondel PM (1993). Human peripheral gamma delta T cells recognize hsp60 molecules on Daudi Burkitt’s lymphoma cells. J Immunol 150:2046–2055.
Kilpi AM (1987). Activation marker analysis of mononuclear cell infiltrates of oral lichen planus in situ. Scand J Dent Res 95:174–180.
Kilpi AM (1988). Characterization of mononuclear cells of inflammatory infiltrates in oral tissues. A histochemical and immunohistochemical study of labial salivary glands in Sjögren’s syndrome and of oral lesions in systemic lupus erythematosus and in lichen planus. Proc Finn Dent Soc 84:5–93.
Kristensen M, Chu CQ, Eedy DJ, Feldmann M, Brennan FM, Breathnach SM (1993). Localization of tumour necrosis factor-alpha (TNF-alpha) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor. Clin Exp Immunol 94:354–362.
Ortiz A, Ziyadeh FN, Neilson EG (1997). Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Invest Med 45:50–56.
Piguet PF, Grau GE, Vesin C, Loetscher H, Gentz R, Lesslauer W (1992). Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology 77:510–514.
Pullan S, Wilson J, Metcalfe A, Edwards GM, Goberdhan N, Tilly J, et al. (1996). Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. J Cell Sci 109:631–642.
Racke MK, Dhib-Jalbut S, Cannella B, Albert PS, Raine CS, McFarlin DE (1991). Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. J Immunol 146:3012–3017.
Rich AM, Reade PC (1989). A quantitative assessment of Langerhans cells in oral mucosal lichen planus and leukoplakia. Br J Dermatol 120:223–228.
Rovere P, Vallinoto C, Bondanza A, Crosti MC, Rescigno M, Ricciardi Castagnoli P, et al. (1998). Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol 161:4467–4471.
Sarkany L, Gaylarde PM (1971). Ultrastructural and light microscopic changes of the epidermo-dermal junction. Trans St John’s Hosp Dermatol Soc 57:139–142.
Schubert MM, Sullivan KM (1990). Recognition, incidence, and management of oral graft-versus-host disease. NCI Monogr 9:135–143.
Sekine C, Yagita H, Miyasaka N, Okumura K (1998). Expression and function of CD40 in rheumatoid arthritis synovium. J Rheumatol 25:1048–1053.
Simark-Mattsson C, Jontell M, Bergenholtz G, Heyden M, Dahlgren UI (1998). Distribution of interferon-gamma mRNA-positive cells in oral lichen planus lesions. J Oral Pathol Med 27:483–488.
Spetz A-L, Strominger J, Groh-Spies V (1996). T cell subsets in normal human epidermis. Am J Pathol 149:665–674.
Sugerman PB, Savage NW, Zhou X, Walsh LJ, Bigby M (2000a). Oral lichen planus. Clin Dermatol 18:533–539.
Walton LJ, Macey MG, Thornhill MH, Farthing PM (1998). Intraepithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus. J Oral Pathol Med 27:116–123.
Williams RO, Feldmann M, Maini RN (1992). Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA 9:9784–9788.
Zhao ZZ, Savage NW, Pujic Z, Walsh LJ (1997). Immunohistochemical localization of mast cells and mast cell-nerve interactions in oral lichen planus. Oral Dis 3:71–76.
Zhou XJ, Savage NW, Sugerman PB, Walsh LJ, Aldred MJ, Seymour GJ (1996). TCR Vβ gene expression in lesional T lymphocyte cell lines in oral lichen planus. Oral Dis 2:295–298.