Hypoxia-Conditioned MSC-Derived Exosomes Mitigate Imiquimod-Induced Psoriasiform Dermatitis by Enhancing FOXP3 Expression and Normalizing Keratin-10 Expression

This study evaluated whether hypoxia-conditioned mesenchymal stem cell–derived exosomes (EH-MSC) mitigate imiquimod (IMQ)-induced psoriasiform dermatitis by enhancing immune regulation and restoring epidermal differentiation. Male Wistar rats (n=32) were used: 30 rats were randomized into five experimental groups (n=6 per group)—healthy control (G1), IMQ + saline (G2), IMQ + methotrexate (G3), IMQ + EH-MSC 100 µL (G4), and IMQ + EH-MSC 200 µL (G5)—and two additional rats were used for model validation. Psoriasiform dermatitis was induced using topical IMQ 5% for 7 days, followed by intradermal treatments (EH-MSC on days 1 and 3 post-validation). EH-MSC exosomes were generated from hypoxia-primed MSC cultures and confirmed by CD63/CD9 markers. Cutaneous FOXP3 and keratin-10 (K10) were quantified by qRT-PCR at the terminal time point. IMQ produced typical psoriasiform plaques and histologic changes. FOXP3 differed significantly among groups (ANOVA p<0.001) and increased dose-dependently with EH-MSC, peaking in G5 (1.84±0.29 pg/mL) versus G2 (0.65±0.33 pg/mL). K10 also differed significantly (p<0.001) and shifted toward healthy levels with EH-MSC, most closely in G5 (1.35±0.71 pg/mL) versus G2 (3.86±0.67 pg/mL). These findings show that EH-MSC treatment was associated with increased FOXP3 expression, suggesting enhanced Treg-associated immunoregulatory activity, and normalization of K10 expression toward healthy control levels.