An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155
Annelinde Terlou, Lindy A M Santegoets, Willem I van der Meijden, Claudia Heijmans-Antonissen, Sigrid M A Swagemakers, Peter J van der Spek, Patricia C Ewing, Marc van Beurden, Theo J M Helmerhorst, Leen J Blok, Annelinde Terlou, Lindy A M Santegoets, Willem I van der Meijden, Claudia Heijmans-Antonissen, Sigrid M A Swagemakers, Peter J van der Spek, Patricia C Ewing, Marc van Beurden, Theo J M Helmerhorst, Leen J Blok
Abstract
Vulvar lichen sclerosus and lichen planus are T-cell-mediated chronic skin disorders. Although autoimmunity has been suggested, the exact pathogenesis of these disorders is still unknown. Therefore, the aim of the current study was to investigate the molecular and immunological mechanisms critical to the pathogenesis of vulvar lichen sclerosus and lichen planus. By using gene expression profiling and real-time RT-PCR experiments, we demonstrated a significantly increased expression of the pro-inflammatory cytokines (IFNγ, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFNγ-induced immune response. In addition, BIC/microRNA-155 (miR-155)--a microRNA involved in regulation of the immune response--was significantly upregulated in lichen sclerosus and lichen planus (9.5- and 17.7-fold change, respectively). Immunohistochemistry showed a significant T-cell response, with pronounced dermal infiltrates of CD4(+), CD8(+), and FOXP3(+) cells. In conclusion, these data demonstrate an autoimmune phenotype in vulvar lichen sclerosus and lichen planus, characterized by increased levels of Th1-specific cytokines, a dense T-cell infiltrate, and enhanced BIC/miR-155 expression.
Source: PubMed