| Background: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.Objective:This study investigated the effects of R848 on ovalbumin(OVA)and rmIL-33 induced BALB/c mice allergic rhinitis(AR),and the undering mechanisms.Methods:BALB/c mice were sensitized with OVA or rmIL-33 to build mice allergic rhiinitis(AR)model,and treated with R848.The nasal symptoms were evaluated by sneezing and nasal rubbing motions count in 15 min after the final rmIL-33 challenge;the eosinophils infiltration and the goblet cell hyperplasia in nasal mucosa were evaluated by hematoxylin and eosin(H & E)and Periodic Acid-Schiff(PAS)staining respectively;the ST2 expression in nasal mucosa were evaluated with immunofluorescence staining(IF);the epithelial cell-derived cytokines including thymic stromal lymphopoietin(TSLP),IL-25,and IL-33 levels in serum of OVA-induced AR mice and IFN-??IL-17 levels in serum of rmIL-33-induced AR mice were measured with enzyme-linked immunosorbent assays(ELISAs);the proportions of Th1?Th2 ? Th17 and Treg cells in the spleen were assessed with flow cytometry,the mRNA expression levels of IFN-?,IL-17 and Foxp3 in the spleen determined by quantitative real-time RT-PCR(q RT-PCR).Results:R848 reduced the IL-25?IL-33 levels in serum?the ST2 expression in nasal mucosa and upregulated the Th1/Th2 ratio in the spleen relative to that in OVA-induced AR mice.In addiction,R848 alleviated the nasal symptoms,reduced the eosinophils infiltration?the goblet cell hyperplasia and ST2 expression in the nasal mucosa compared with that in rmIL-33-induced AR mice,and reverse the lymphocyte differentiation,serum inflammatory cytokines production and their local mRNA expression level in nasal mucosa in rmIL-33 stimulated mice.Conclusion:R848 suppresses IL-33/ST2 signal,which may contribute to its anti-allergic effects. |
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