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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents

ID: 558412.0, MPI für Neurobiologie / Neuroimmunology
Neutrophils Require SHP1 To Regulate IL-1 beta Production and Prevent Inflammatory Skin Disease
Authors:Croker, B. A.; Lewis, R. S.; Babon, J. J.; Mintern, J. D.; Jenne, D. E.; Metcalf, D.; Zhang, J. G.; Cengia, L. H.; O'Donnell, J. A.; Roberts, A. W.
Date of Publication (YYYY-MM-DD):2011-01-15
Title of Journal:Journal of Immunology
Journal Abbrev.:J. Immunol.
Issue / Number:2
Start Page:1131
End Page:1139
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:The regulation of neutrophil recruitment, activation, and disposal is pivotal for circumscribed inflammation. SHP1(Y208N/Y208N) mutant mice develop severe cutaneous inflammatory disease that is IL-1R dependent. Genetic reduction in neutrophil numbers and neutrophilic responses to infection is sufficient to prevent the spontaneous initiation of this disease. Neutrophils from SHP1(Y208N/Y208N) mice display increased pro-IL-1 beta production due to altered responses to MyD88-dependent and MyD88-independent signals. The IL-1R-dependent inflammatory disease in SHP1(Y208N/Y208N) mice develops independently of caspase 1 and proteinase 3 and neutrophil elastase. In response to Fas ligand, a caspase 1-independent inducer of IL-1 beta production, neutrophils from SHP1(Y208N/Y208N) mice produce elevated levels of IL-1 beta but display reduced caspase 3 and caspase 7 activation. In neutrophils deficient in SHP1, IL-1 beta induces high levels of pro-IL-1 beta suggesting the presence of a paracrine IL-1 beta loop. These data indicate that the neutrophil-and IL-1-dependent disease in SHP1(Y208N/Y208N) mice is a consequence of loss of negative regulation of TLR and IL-1R signaling. The Journal of Immunology, 2011, 186: 1131-1139.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
External Affiliations:[Croker, Ben A.; Lewis, Rowena S.; Babon, Jeff J.; Metcalf, Donald; Zhang, Jian-Guo; Cengia, Louise H.; O'Donnell, Joanne A.; Roberts, Andrew W.] Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Parkville, Vic 3052, Australia.; [Croker, Ben A.; Babon, Jeff J.; Metcalf, Donald; Roberts, Andrew W.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.; [Croker, Ben A.] Scripps Res Inst, Dept Genet, La Jolla, CA 92037 USA.; [Babon, Jeff J.] Walter & Eliza Hall Inst Med Res, Struct Biol Div, Parkville, Vic 3052, Australia.; [Mintern, Justine D.] Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3052, Australia.; [Roberts, Andrew W.] Univ Melbourne, Fac Med, Parkville, Vic 3010, Australia.
Identifiers:ISI:000285917700052 [ID No:1]
ISSN:0022-1767 [ID No:2]
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