911 Mature interleukin-36γ induces epidermal stratum corneum exfoliation in generalized pustular psoriasis via downregulation of corneodesmosine

Loss-of-function mutations in the IL36RN gene encoding interleukin-36 receptor antagonist (IL-36RA) cause familial generalized pustular psoriasis (GPP), which often begins shortly after birth and is difficult to treat. Previously, we found that IL-36 agonists, especially mature IL-36γ, promote production of IL-8 proIL-36γ epidermis simultaneously downregulate genes for epidermal keratinocyte envelope-related proteins such as corneodesmosin (CDSN). In present study, expression highly downregulated under Kogoj’s spongiform pustules GPP patients. Specifically, immunofluorescent staining two patients with compound heterozygous (c.[115+6T>C];[125T>A]) homozygous mutation (c.115+6T>C) revealed a significant 7-fold decrease percentage subcorneal pustule sites compared healthy controls without (one-way analysis variance Tukey's multiple comparison test, p <0.0001). Previous reports have already shown upregulated, our immunofluorescence data also showed higher control. It widely known cleaved its form by proteases elastase cathepsin G produced neutrophils. data, except area Kogoj's pustules, suggesting neutrophils infiltrating may produce convert suppress corneodesmosin. Epidermis reduced would experience more widespread stratum corneum exfoliation, leading formation increasingly large pustules. These findings provide insight into mechanism GPP.