Dulce Soler-Ferran1, Fabiola Louis2, Sook-Bin Woo3,4, Steven A Greenberg5. 1. Abcuro, Inc, Newton, MA, USA. 2. Histowiz, Inc, Brooklyn, NY, USA. 3. Center for Oral Pathology, StrataDx, Lexington, MA, USA. 4. Harvard School of Dental Medicine, Boston, MA, USA. 5. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, and Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. sagreenberg@bwh.harvard.edu.
Abstract
BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease affecting oral mucosa. Its pathogenesis includes T cell infiltration. T cells may be naïve or in response to antigen stimulation, progress through differentiation stages. The differentiated states of T cells in OLP mucosa have not previously been reported. METHODS: Available OLP microarray gene expression data from Gene Expression Omnibus were analyzed for markers of T cell cytotoxicity. Immunohistochemical studies of T cell subset markers CD4 and CD8 and the T cell differentiation marker killer cell lectin-like receptor G1 (KLRG1) were performed on paraffin embedded formalin fixed oral mucosa biopsy samples from 10 patients with OLP. RESULTS: Gene expression analysis of OLP oral mucosa samples disclosed increased transcript expression of KLRG1, CD8A, and granzyme K (GZMK). By immunohistochemistry, prominent CD4 + and CD8 + T cell infiltration was seen in all patient samples. KLRG1 + T cells were abundant, constituting a mean of 51% (range 40-65%) of the number of CD8 + T cells. KLRG1 + T cells localized at the epithelium and lamina propria junction, infiltrating both basal and intraepithelial regions and adjacent to both basal and intraepithelial keratinocytes. CONCLUSIONS: OLP oral mucosa T cell infiltration includes KLRG1 + highly differentiated cytotoxic T cells, suggesting continued antigen exposure driving T cells to a highly differentiated phenotype. The known phenotype of these cells, together with microarray detected increases in cytotoxic molecules, suggests that highly differentiated cytotoxic T cells contribute to oral mucosa injury in OLP.
BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease affecting oral mucosa. Its pathogenesis includes T cell infiltration. T cells may be naïve or in response to antigen stimulation, progress through differentiation stages. The differentiated states of T cells in OLP mucosa have not previously been reported. METHODS: Available OLP microarray gene expression data from Gene Expression Omnibus were analyzed for markers of T cell cytotoxicity. Immunohistochemical studies of T cell subset markers CD4 and CD8 and the T cell differentiation marker killer cell lectin-like receptor G1 (KLRG1) were performed on paraffin embedded formalin fixed oral mucosa biopsy samples from 10 patients with OLP. RESULTS: Gene expression analysis of OLP oral mucosa samples disclosed increased transcript expression of KLRG1, CD8A, and granzyme K (GZMK). By immunohistochemistry, prominent CD4 + and CD8 + T cell infiltration was seen in all patient samples. KLRG1 + T cells were abundant, constituting a mean of 51% (range 40-65%) of the number of CD8 + T cells. KLRG1 + T cells localized at the epithelium and lamina propria junction, infiltrating both basal and intraepithelial regions and adjacent to both basal and intraepithelial keratinocytes. CONCLUSIONS: OLP oral mucosa T cell infiltration includes KLRG1 + highly differentiated cytotoxic T cells, suggesting continued antigen exposure driving T cells to a highly differentiated phenotype. The known phenotype of these cells, together with microarray detected increases in cytotoxic molecules, suggests that highly differentiated cytotoxic T cells contribute to oral mucosa injury in OLP.
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