Distinct role of IL-1β in instigating disease in Sharpin cpdm mice

Prajwal Gurung; Bhesh Raj Sharma; Thirumala-Devi Kanneganti

doi:10.1038/srep36634

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Distinct role of IL-1β in instigating disease in Sharpin cpdm mice

Journal article

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Distinct role of IL-1β in instigating disease in Sharpin cpdm mice

Prajwal Gurung, Bhesh Raj Sharma and Thirumala-Devi Kanneganti

Scientific reports, Vol.6, p.36634

11/28/2016

DOI: 10.1038/srep36634

PMCID: PMC5125001

PMID: 27892465

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Abstract

Mice deficient in SHARPIN (Sharpin 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 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 Sharpin 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 Sharpin mice. Our results altogether demonstrate distinct roles of SHARPIN in initiating systemic inflammation and dermatitis. Furthermore, skin inflammation in Sharpin mice is specifically modulated by IL-1β, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade.

Details

Title: Subtitle: Distinct role of IL-1β in instigating disease in Sharpin cpdm mice
Creators: Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
Bhesh Raj Sharma - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.6, p.36634
DOI: 10.1038/srep36634
PMID: 27892465
PMCID: PMC5125001
NLM abbreviation: Sci Rep
eISSN: 2045-2322
Grant note: R01 AI101935 / NIAID NIH HHS P30 CA021765 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS R01 CA163507 / NCI NIH HHS R01 AI124346 / NIAID NIH HHS
Language: English
Date published: 11/28/2016
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094581802771

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