The pathogenesis of oral lichen planus.
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-beta1-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-alpha, 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-beta 1, TNF-alpha, IFN-gamma, 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.
AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. philip.sugerman@astrazeneca.com
P B
PB
Sugerman
N W
NW
Savage
L J
LJ
Walsh
Z Z
ZZ
Zhao
X J
XJ
Zhou
A
A
Khan
G J
GJ
Seymour
M
M
Bigby
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D017676:Lichen Planus, Oral / Q000276:immunology*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha