T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease.
Blood
; 103(9): 3457-64, 2004 May 01.
Article
em En
| MEDLINE
| ID: mdl-14726372
ABSTRACT
The deregulation of the immune response is a critical component in inflammatory disease. Recent in vitro data show that T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of cytokine signaling. Furthermore, tc-ptp(-/-) mice display immune defects and die within 5 weeks of birth. We report here that tc-ptp(-/-) mice develop progressive systemic inflammatory disease as shown by chronic myocarditis, gastritis, nephritis, and sialadenitis as well as elevated serum interferon-gamma. The widespread mononuclear cellular infiltrates correlate with exaggerated interferon-gamma, tumor necrosis factor-alpha, interleukin-12, and nitric oxide production in vivo. Macrophages grown from tc-ptp(-/-) mice are inherently hypersensitive to lipopolysaccharide, which can also be detected in vivo as an increased susceptibility to endotoxic shock. These results identify T-cell protein tyrosine phosphatase as a key modulator of inflammatory signals and macrophage function.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Proteínas Tirosina Fosfatases
/
Mediadores da Inflamação
/
Inflamação
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Canadá