Expression of lymphotoxin-alpha by keratinocytes: A further mediator for the lichenoid reaction

Objective: Lichen planus (LP) represents a disease in which autoimmune mech anisms mediated by Th1 T cells are involved. Lymphotoxin-alpha (LT-alpha) r epresents a Th1 cytokine with proinflammatory activities in LP, as has rece ntly been demonstrated for interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Methods: Expression of LT-alpha mRNAwas investiga ted by RT-PCR and nonradioactive in situ hybridization. Double staining met hods were applied to characterize the phenotype of cells expressing LT-alph a. Cell stimulation experiments were performed on the transformed squamous cell line HaCaT. Results: In contrast to normal skin, LT-alpha -specific RT -PCR products were found in all cases of LP. Cells in the inflammatory infi ltrate expressing LT-alpha were identified as mainly T cells and mast cells , as shown by in situ hybridization. Furthermore, predominant LT-alpha mRNA expression could be observed in lesional keratinocytes adjacent to the ban d-like inflammatory infiltrate. In cell stimulation experiments, it could b e shown that IFN-gamma induces LT-alpha and TNF-alpha mRNA in the human squ amous cell line HaCaT, concomitant with upregulation of MHC class II and in tercellular adhesion molecule-1, which could also be observed on lesional k eratinocytes in LP. Conclusions: In LP, LT-alpha mRNA is predominantly expr essed by lesional keratinocytes and to a lesser extent by inflammatory cell s. Induction of LT-alpha in keratinocytes is closely related to the express ion of TNF-alpha and MHC class II. The loci of TNF-alpha and LT-alpha map t o MHC class III on chromosome 6, which is closely linked to the MHC class I I gene locus. Our results suggest that stimulation of keratinocytes with IF N-gamma results in the upregulation of proinflammatory cytokines such as LT -alpha and TNF-alpha as well as MHC class 11, which map to the same gene re gion of immunoregulatory genes on chromosome 6 and may be involved in the i nduction and maintenance of the disease. Copyright (C) 2001 S. Karger AG, B asel.