In the present study, an imiquimod-induced psoriasis-like dermatitis mouse model was constructed under natural immune conditions and verified by evaluations of the Psoriasis Area and Severity Index (PASI) score and Baker score, H&E staining, immunohistochemical examination of the CD3 and Gr1 levels, measurement of plasmacytoid dendritic cell- (pDC) and Th17-associated cytokine levels, and evaluation of p65 phosphorylation and TLR7 expression.
Using an <i>in vivo</i> model of tolerance to TLR7-induced skin inflammation, we found a critical role for macrophage-derived MMP10 in mediating immune hypo-responsiveness.
In addition, we found that rhododendrin inhibits the activation of the TLR-7/NF-κB and mitogen-activated protein kinase pathways in both IMQ-induced psoriasis-like skin inflammation in mice and in normal human epidermal keratinocytes treated with IMQ.
In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis.