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.

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“…Physiologically, FAP-α declines with age but its expression is up-regulated in cardiovascular diseases (Tillmanns et al, 2015), pulmonary fibrosis (Fan et al, 2016), cancer (Wen et al, 2017) as well as in oral diseases such as human oral squamous cell carcinoma (Wu et al, 2020) and oral lichen planus (Y. Zhang et al, 2022). We found significantly increased levels of FAP-α in periodontally involved sites compared with healthy controls.…”

“…This marker, also known as seprase, is a type II membrane serine protease that promotes type I collagen degradation (Chung et al, 2014); its expression regulates connective tissue re‐modelling and is linked with levels of TGF‐β1 and IL‐1β (Tillmanns et al, 2015). Physiologically, FAP‐α declines with age but its expression is up‐regulated in cardiovascular diseases (Tillmanns et al, 2015), pulmonary fibrosis (Fan et al, 2016), cancer (Wen et al, 2017) as well as in oral diseases such as human oral squamous cell carcinoma (Wu et al, 2020) and oral lichen planus (Y. Zhang et al, 2022). We found significantly increased levels of FAP‐α in periodontally involved sites compared with healthy controls.…”

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“…Examples of microscopic descriptions include skin associated with hypogranulosis, hyperkeratosis, and vacuolar basal change. This also involves specifying whether the skin dermis demonstrates band-like patterns of lymphocytic infiltration, pigment incontinence, and other info pertaining to stains [6][7][8]. Such descriptions provide a more accurate diagnosis if the skin lesion is related to LP.…”

Is roflumilast a feasible alternative for the treatment of mucocutaneous lichen?

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Oral lichen planus (OLP) is a chronic inflammatory disease mainly mediated by lymphocytes. 1 Involvement of the dorsal aspect of the tongue is less common than other localisations. When symptomatic, it can have a significant impact on a patient's quality of life.

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