FAP-α+ immunofibroblasts in oral lichen planus promote CD4+ T-cell infiltration via CCL5 secretion.

ABSTRACT

Oral lichen planus (OLP) is a T cell-mediated, chronic inflammatory disease. CD4+ T-cell infiltration plays a crucial role in the pathogenesis of OLP. Fibroblasts are activated under pathological conditions and perform various functions. This study was designed to explore the immune activation and biological functions of OLP fibroblasts on CD4+ T cells. We detected the expression of fibroblast activation protein-alpha (FAP-α) in the oral tissues of patients with OLP and healthy controls using immunohistochemistry. Furthermore, expression of FAP-α and C-C motif chemokine ligand 5 (CCL5) in fibroblasts isolated from oral tissues of patients with OLP and healthy controls was assayed by quantitative PCR, Western blotting and enzyme-linked immunosorbent assay. Moreover, we assessed the effects of fibroblasts on CD4+ T-cell proliferation, apoptosis and migration using flow cytometry and Transwell assays. We found that FAP-α expression in the oral tissues of patients with OLP was significantly higher than that in healthy controls. FAP-α and CCL5 expression levels were significantly upregulated in OLP fibroblasts. Moreover, OLP fibroblasts promoted CD4+ T-cell proliferation and migration and inhibited CD4+ T cell apoptosis. In summary, our findings indicate that OLP fibroblasts are immunologically activated and induce CD4+ T-cell infiltration in OLP.