The effects of resiquimod in an ovalbumin-induced allergic rhinitis model

Abstract

Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice. Histological changes in the nasal mucosa were evaluated by hematoxylin and eosin (H & E) and Periodic Acid-Schiff (PAS) staining; cytokine levels in serum were measured with enzyme-linked immunosorbent assays (ELISAs);the mRNA expression levels of IFN-γ, IL-17 and Foxp3 in the spleen determined by quantitative real-time RT-PCR (qRT-PCR); the proportions of Th1, Th2, Th17, Treg and TIM3 + IFN-γ + Th1 cells in the spleen were assessed with flow cytometry; TIM1, TIM3 and IL-33 expression levels in the nasal mucosa were evaluated with immunofluorescence staining(IF).R848 alleviated the nasal allergic symptoms; reduced eosinophil cell infiltration, goblet cell hyperplasia in the nasal mucosa; reduced IL-13, IL-17, IL-25 and IL-33 levels in serum; upregulated the relative mRNA expression of IFN-γ and Foxp3, and downregulated the relative mRNA expression of IL-17 in the spleen; decreased Th2, Th17 and TIM3 + IFN-γ + Th1 cells ratios, increased the proportion of Th1 and Treg cells in the spleen; suppressed TIM1 and TIM3,but increased IL-33 expression in the nasal mucosa in OVA-induced AR mice. R848 suppresses IL-25, IL-33 released and TIM1, TIM3 expression, which may contribute to its anti-allergic effects.