| First Author | Gurung P | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 36634 | PubMed ID | 27892465 |
| Mgi Jnum | J:295919 | Mgi Id | MGI:6223208 |
| Doi | 10.1038/srep36634 | Citation | Gurung P, et al. (2016) Distinct role of IL-1beta in instigating disease in Sharpin(cpdm) mice. Sci Rep 6:36634 |
| abstractText | 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-1alpha or IL-1beta, 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-1beta, but not IL-1alpha, 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-1beta, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade. |
