Neutrophils require SHP1 to regulate IL-1ß production and prevent inflammatory skin disease.
J Immunol
; 186(2): 1131-9, 2011 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-21160041
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-1ß 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-1ß production, neutrophils from SHP1(Y208N/Y208N) mice produce elevated levels of IL-1ß but display reduced caspase 3 and caspase 7 activation. In neutrophils deficient in SHP1, IL-1ß induces high levels of pro-IL-1ß suggesting the presence of a paracrine IL-1ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dermatopatias
/
Mediadores da Inflamação
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Proteína Tirosina Fosfatase não Receptora Tipo 6
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Interleucina-1beta
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Neutrófilos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália