Atopic dermatitis (AD) and psoriasis (PS) are inflammatory skin diseases and one of the features of AD is dominant colonization with Staphylococcus aureus (S. aureus). Inflammasomes are protein complexes that contribute to host defense against pathogens and cleave the cytokines pro-interleukin (IL)-1β and pro-IL-18 into their secreted active forms. In the current study, we measured the expression of IL-1 family members and inflammasome components in the skin of PS and AD patients and studied their regulation by cytokines, S. aureus and S. epidermidis in human primary keratinocytes by RT-qPCR, ELISA, and immunofluorescence. We show that the expression of IL1B and IL18 is increased in the lesional skin of PS and AD patients, respectively, while inflammasome components, NLRP1, NLRP3, PYCARD, and CASP1 are increased in these diseases. A positive relationship between NLRP1 and IL1B was found both in AD and PS, but between NLRP1 and IL18 expression, only in AD. Accordingly, increased caspase-1 activity in the skin of AD patients was detected. Interestingly, in keratinocytes, the inoculation with S. aureus, but neither S. epidermidis nor tested cytokines led to the increased secretion of IL-1β and IL-18. In addition, we performed colocalization analysis using datasets from two GWAS and 112 eQTL studies to identify variants that are associated with AD and can alter gene expression. Among 148 genes identified to be associated with AD, we detected IL1RL1, IL18, IL18R1, IL18RAP as AD-related genes with expression in multiple immune-system-related cell types. Together, our data indicate the increased inflammasome activation in the skin of AD patients, which could be a result of higher levels of inflammasome genes in the skin, colonization with S. aureus, and genetic variations in the IL-1 family cytokines and their receptors.

ESDR222 - Skin colonization with S. aureus can lead to increased inflammasome activation in patients with atopic dermatitis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING