1559 Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis

Protein Phosphatase 6 down-regulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits psoriasis, indicating restoration of protein phosphatase can be rational strategy for psoriasis treatment. Through phenotypic screen, we here identify L-menthol ameliorates psoriasis-like skin inflammation by increasing keratinocytes. Target identification approaches reveal an indispensable role transcription factor hairy and enhancer split 1 governing 6-upregulating function The diminished epidermis patients imiquimod-induced mouse model, while upregulates preventing its proteasomal degradation. Mechanistically, transcriptionally activates expression immunoglobulin-binding which promotes inhibits ubiquitination. Collectively, discover therapeutic compound, L-menthol, uncover dysfunctional 1- axis contributes to pathology using as probe.