title: Distinct role of IL-1β in instigating disease in Sharpincpdmmice.
abstract: Mice deficient in SHARPIN (Sharpincpdmmice), 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 Sharpincpdmmice. 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 Sharpincpdmmice 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 Sharpincpdmmice. Our results altogether demonstrate distinct roles of SHARPIN in initiating systemic inflammation and dermatitis. Furthermore, skin inflammation in Sharpincpdmmice is specifically modulated by IL-1β, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Prajwal
authors.initials: P
authors.lastname: Gurung
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Bhesh Raj
authors.initials: BR
authors.lastname: Sharma
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; C554944:Sipl1 protein, mouse