What is the pathophysiology of oral lichen planus (OLP)?

Updated: Sep 15, 2020
  • Author: Jaisri R Thoppay, DDS, MBA, MS; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Current data suggest that oral lichen planus (OLP) is a T-cell–mediated autoimmune disease in which autocytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. [1, 2, 3]

The dense subepithelial mononuclear infiltrate in oral lichen planus is composed of T cells and macrophages, and there are increased numbers of intraepithelial T cells. Most T cells in the epithelium and adjacent to the damaged basal keratinocytes are activated CD8+ lymphocytes. Therefore, early in the formation of oral lichen planus lesions, CD8+ T cells may recognize an antigen associated with the major histocompatibility complex (MHC) class I on keratinocytes. After antigen recognition and activation, CD8+ cytotoxic T cells may trigger keratinocyte apoptosis. Activated CD8+ T cells (and possibly keratinocytes) may release cytokines that attract additional lymphocytes into the developing lesion. [2]

Oral lichen planus lesions contain increased levels of the cytokine tumor necrosis factor (TNF)–alpha. [4, 5] Basal keratinocytes and T cells in the subepithelial infiltrate express TNF in situ. [6, 7] Keratinocytes and lymphocytes in cutaneous lichen planus express elevated levels of the p55 TNF receptor, TNF-RI. [8] T cells in oral lichen planus contain mRNA for TNF and secrete TNF in vitro. [9] Serum and salivary TNF levels are elevated in oral lichen planus patients. [10, 11, 12, 13] TNF polymorphisms have been identified in patients with oral lichen planus, and they may contribute to the development of additional cutaneous lesions. [14] Oral lichen planus has been treated successfully with thalidomide, [15, 16] a drug known to suppress TNF production. [17, 18] Together, these data implicate TNF in the pathogenesis of oral lichen planus.

Of possible significance, elevated concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with the erosive-atrophic form of oral lichen planus suggest they may be involved in the etiology of this disease variation. [19] Research published in 2015 also suggests that osteopontin, CD44, and survivin may be involved in the pathogenesis of oral lichen planus. [20] Additionally, microRNA 4484 (miR-4484) has been found to be significantly up-regulated in the salivary exosomes of patients with oral lichen planus. [21]

The specific antigen that triggers lichen planus is unknown, although it may be a self-peptide (or altered self-peptide), in which case lichen planus would be a true autoimmune disease. The role of autoimmunity in the pathogenesis is supported by many autoimmune features of oral lichen planus, including its chronicity, onset in adults, predilection for females, association with other autoimmune diseases, occasional tissue-type associations, depressed immune-suppressor activity in patients with oral lichen planus, and the presence of autocytotoxic T-cell clones in lichen planus lesions. The expression or unmasking of the lichen planus antigen may be induced by drugs (lichenoid drug reaction), contact allergens in dental restorative materials or toothpastes (contact hypersensitivity reaction), mechanical trauma (Koebner phenomenon), viral infection, or other unidentified agents. [22, 23, 24]

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