Paeoniflorin drives the immunomodulatory effects of mesenchymal stem cells by regulating Th1/Th2 cytokines in oral lichen planus

Lichen planus (LP) is a chronic inflammatory disease. Oral lichen planus (OLP) mainly appears as oral mucosal reticular or ulcerative lesions with an unknown etiology. We aimed to explore the immunomodulatory effect of paeoniflorin (PF) in mesenchymal stem cells (MSCs) and the potential involvement of Th1/Th2 cytokines in OLP. The effects of paeoniflorin on the proliferation and migration of MSCs were detected by Cell Counting Kit-8 (CCK8) and Transwell assays. MSCs were subjected to osteogenic, adipogenic and neurogenic induction followed by Alizarin red, oil red O, real-time PCR and immunofluorescence assays. We found that paeoniflorin promoted the proliferation, migration and multilineage differentiation of MSCs from OLP lesions (OLP-MSCs) in vitro. Paeoniflorin pretreatment increased the inhibitory effect of OLP-MSCs on peripheral blood mononuclear cells. Furthermore, paeoniflorin-pretreated OLP-MSCs simultaneously decreased Th1 cytokine levels and increased Th2 cytokine levels in T lymphocyte cocultures. Finally, paeoniflorin-pretreated OLP-MSCs also promoted the Th1/Th2 balance both in vitro and in the serum of mice that received skin allografts. In conclusion, paeoniflorin enhanced MSC immunomodulation and changed the inflammatory microenvironment via T lymphocytes, suggesting that the improvement of OLP-MSCs is a promising therapeutic approach for OLP.