Distinct role of IL-1? in instigating disease in Sharpin^cpdm mice.

ABSTRACT: Mice deficient in SHARPIN (Sharpin^cpdm mice), a member of linear ubiquitin chain assembly complex (LUBAC), develop severe dermatitis associated with systemic inflammation. Previous studies have demonstrated that components of the TNF-signaling pathway, NLRP3 inflammasome and IL-1R signaling are required to provoke skin inflammation in Sharpin^cpdm mice. However, whether IL-1? or IL-1?, both of which signals through IL-1R, instigates skin inflammation and systemic disease is not known. Here, we have performed extensive cellular analysis of pre-diseased and diseased Sharpin^cpdm mice and demonstrated that cellular dysregulation precedes skin inflammation. Furthermore, we demonstrate a specific role for IL-1?, but not IL-1?, in instigating dermatitis in Sharpin^cpdm mice. Our results altogether demonstrate distinct roles of SHARPIN in initiating systemic inflammation and dermatitis. Furthermore, skin inflammation in Sharpin^cpdm mice is specifically modulated by IL-1?, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade.

SUBMITTER: Gurung P 

PROVIDER: S-EPMC5125001 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature