Year: 2016
Type: article
Abstract: Mice deficient in SHARPIN (Sharpincpdm 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 Sharpincpdm mice. However, whether IL-1α or IL-1β, 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 Sharpincpdm mice and demonstrated that cellular dysregulation precedes skin inflammation. Furthermore, we demonstrate a specific role for IL-1β, but not IL-1α, in instigating dermatitis in Sharpincpdm mice. Our results altogether demonstrate distinct roles of SHARPIN in initiating systemic inflammation and dermatitis. Furthermore, skin inflammation in Sharpincpdm mice is specifically modulated by IL-1β, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade.
Source: Scientific Reports
DOI: 10.1038/srep36634
Institution: St. Jude Children's Research Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G137859075, Role of IL-1alpha signaling in inflammatory diseases and host defense, G3831755428, G4358640472, G4533544333, G4766096375, G4869702982, G5372223083, Inflammatory Caspases in Innate Immunity and Inflammation, G8167955467, Innate immune signaling and stress response, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2558630341