Neutrophils Require SHP1 To Regulate IL-1 beta Production and Prevent Inflammatory Skin Disease
- Author(s)
- Croker, BA; Lewis, RS; Babon, JJ; Mintern, JD; Jenne, DE; Metcalf, D; Zhang, JG; Cengia, LH; O'Donnell, JA; Roberts, AW;
- Details
- Publication Year 2011-01-15,Volume 186,Issue #2,Page 1131-1139
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- MOTH-EATEN MICE; NECROSIS-FACTOR-ALPHA; TYROSINE-PHOSPHATASE; GENE-EXPRESSION; RESPIRATORY BURST; INFLUENZA-VIRUS; CELL LYMPHOMA; DEATH DOMAIN; MUTANT MICE; NPM-ALK
- Research Division(s)
- Cancer And Haematology; Structural Biology; Immunology
- Publisher's Version
- https://doi.org/10.4049/jimmunol.1002702
- Terms of Use/Rights Notice
- Copyright © 2011 by The American Association of Immunologists, Inc.
Creation Date: 2011-01-15 12:00:00
Last Modified: 2014-12-23 12:06:25