Indirect inhibition of Toll-like receptor and type I interferon responses by ITAM-coupled receptors and integrins.
Immunity
; 32(4): 518-30, 2010 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-20362473
ABSTRACT
An important function of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors is cross-regulation of heterologous receptor signaling, but mechanisms of cross-inhibition are poorly understood. We show that high-avidity ligation of ITAM-coupled beta2 integrins and FcgammaRs in macrophages inhibited type I interferon receptor and Toll-like receptor (TLR) signaling and induced expression of interleukin-10 (IL-10); signaling inhibitors SOCS3, ABIN-3, and A20; and repressors of cytokine gene transcription STAT3 and Hes1. Induction of inhibitors was dependent on a pathway composed of signaling molecules DAP12, Syk, and Pyk2 that coupled to downstream kinases p38 and MSKs and required integration of IL-10-dependent and -independent signals. ITAM-induced inhibitors abrogated TLR responses by cooperatively targeting distinct steps in TLR signaling. Inhibitory signaling was suppressed by IFN-gamma and attenuated in inflammatory arthritis synovial macrophages. These results provide an indirect mechanism of cross-inhibition of TLRs and delineate a signaling pathway important for deactivation of macrophages.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
/
Interferon Tipo I
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Antígenos CD18
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Receptores Toll-Like
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos