Anti-IL-17A ssDNA aptamer ameliorated psoriasis skin lesions in the imiquimod-induced psoriasis mouse model

Abstract

ObjectivesIL-17 is an important player in the psoriasis pathogenesis, which recruits inflammatory cells to the psoriatic lesions, induced keratinocyte proliferation and plaque formation. Three monoclonal antibodies that block IL-17 have been approved for psoriasis treatment in the last decade. Compared to monoclonal antibodies, aptamers which are single-stranded DNA or RNA, bind with high affinity to proteins or other molecules and are more cost-effective. We previously showed that M2 and M7 anti-IL17A ssDNA aptamers could block IL-17 in vitro. The current study evaluated the therapeutic effects of M2 and M7 anti-IL17A ssDNA aptamers in the imiquimod (IMQ)-induced psoriasis mouse model. MethodsIMQ cream and Vaseline (Vas) were administered on the back skin of C57BL/6 mice as IMQ-induced psoriasis and Vas control groups, respectively. In addition, hydrogel-containing aptamers were topically administered on the back skin of the mice, 10 min before IMQ treatment. Psoriatic lesions were evaluated by histology, clinical factors, and psoriasis area severity index (PASI) score. The mRNA expression levels of inflammatory factors, including IL-17A, IL-1β, and S100a9, were assessed with quantitative reverse transcriptase-polymerase chain reaction in the mice back skin. ResultsApplication of anti-IL-17A aptamers significantly ameliorated IMQ-induced keratinocyte proliferation, psoriatic lesions cumulative PASI score, IL-17A, IL-β, and S100a9 inflammatory factors mRNA expression levels (p < 0.05). ConclusionAccording to our results, it seems that M2 in high concentration and M7 in low concentration can be appropriate candidates to alleviate psoriasis lesions.