TRAIL-R as a negative regulator of innate immune cell responses.
Immunity
; 21(6): 877-89, 2004 Dec.
Article
em En
| MEDLINE
| ID: mdl-15589175
ABSTRACT
TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R(-/-) mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R(-/-) mice exhibited increased clearance of murine cytomegalovirus that correlated with increased levels of IL-12, IFN-alpha, and IFN-gamma. Stimulation of macrophages with Mycobacterium and Toll-like receptor (TLR)-2, -3, and -4, but not TLR9, ligands resulted in high levels of TRAIL upregulation and enhanced cytokine production in TRAIL-R(-/-) cells. The immediate-early TLR signaling events in TRAIL-R(-/-) macrophages and dendritic cells are normal, but I kappa B-alpha homeostatic regulation and NF-kappa B activity at later time points is perturbed. These data suggest that TRAIL-R negatively regulates innate immune responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores do Fator de Necrose Tumoral
/
Imunidade Inata
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article