TY - JOUR
T1 - An Autoimmune Phenotype in Vulvar Lichen Sclerosus and Lichen Planus: A Th1 Response and High Levels of MicroRNA-155
AU - Terlou, Annelinde
AU - Santegoets, Lindy
AU - van der Meijden, WI
AU - Antonissen, Claudia
AU - Swagemakers, Sigrid
AU - van der Spek, Peter
AU - Ewing, PC
AU - van Beurden, M
AU - Helmerhorst, null
AU - Blok, Leen
PY - 2012
Y1 - 2012
N2 - 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 (IFN gamma, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFN gamma-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.
AB - 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 (IFN gamma, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFN gamma-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.
U2 - 10.1038/jid.2011.369
DO - 10.1038/jid.2011.369
M3 - Article
C2 - 22113482
SN - 0022-202X
VL - 132
SP - 658
EP - 666
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -