Abstract
It is well known that psoriasis is closely related to smoking, and CHRNA5 plays an important role in smoking-related diseases. However, studies on the relationship between CHRNA5 and psoriasis are limited. This study aimed to examine the role of CHRNA5 in psoriasis development and pathogenesis. Analysis in psoriatic tissues and imiquimod-induced mouse models showed that CHRNA5 was highly expressed in psoriatic lesional skin. To further verify the function of CHRNA5, we constructed Chrna5-knockout mice and induced the psoriasis model. We found that Chrna5 knockout significantly reduced the severity of psoriasis and could regulate inflammation through the MAPK kinase kinase-1/c-Jun N-terminal kinase‒MAPK/NF-κB pathway. The single-cell sequencing results revealed that after Chrna5 knockout, the keratinocyte subpopulation was significantly reduced and the related Jak/signal transducer and activator of transcription signaling pathway was downregulated, further indicating the importance of CHRNA5 in psoriasis. Human keratinocytes were analyzed, and silencing CHRNA5 inhibited keratinocyte proliferation and migration. In summary, CHRNA5 played important roles in the development and pathogenesis of psoriasis, and targeting CHRNA5 may be an effective strategy for the treatment of psoriasis.