Inflammasome activation is needed for the production of IL-1 family cytokines IL-1β and IL-18. Both these cytokines have been suggested to influence inflammatory responses in AD, as well as genetic association of AD with polymorphisms in the IL18R1 and IL18RAP genes has been proposed. In this study, we report the increased expression of inflammasome sensor NACHT, LRR, and PYD domains-containing protein 1 (NLRP1) and adapter PYD and CARD Domain Containing (PYCARD), as well as mRNA levels of IL1B and IL18 in lesional skin of AD patients. Moreover, we also found a positive relationship between mRNA expression of NLRP1 and IL1B or IL18 and increased caspase-1 activity in the skin of AD patients. Interestingly, in human primary keratinocytes and reconstituted epidermis, the tested AD-related cytokines induced mRNA levels of IL1B and IL18, while none of these cytokines affected the production of IL-1β and IL-18. However, when keratinocytes were stimulated with the same cytokines and infected with AD-related pathogen Staphylococcus (S.) aureus, the secretion of IL-1β and IL-18 was significantly increased, while siRNA silencing of NLRP1 inhibited the production of IL-1β and IL-18. In addition, genetic association and colocalization analysis of published GWAS and eQTL datasets confirmed association of the IL18R1 and IL18RAP genes with AD and revealed that these two genes are mainly expressed in various types of immune cells indicating that IL-18 produced by keratinocytes may also affect the development of AD. In conclusion, our data demonstrate that skin colonization with S. aureus can cause the activation of the NLRP1-dependent inflammasome, while AD-related cytokines may contribute with the stimulation of inflammasome-related genes at mRNA level. In addition, our results suggest that patients with genetic variations in the IL-18 pathway may be affected more by S. aureus infection.

ESDR319 - S. aureus can induce NLRP1 inflammasome activation in patients with atopic dermatitis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.