Human plasmacytoid dendritic cells regulate IFN-α production through activation-induced splicing of IL-18Rα.
J Leukoc Biol
; 96(6): 1037-46, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25170117
ABSTRACT
IFN-α production by pDCs regulates host protection against viruses and is implicated in autoimmune pathology. Human pDCs express high levels of IL-18R, but little is known of its role in pDC function. We report that IL-18R signaling negatively regulates IFN-α production through activation-induced splicing of IL-18Rα in human pDCs. Our data reveal two distinct isoforms of IL-18Rα in human pDCs the known, full-length receptor (IL-18Rα1) and a novel, truncated variant (IL-18Rα2), which functions as a molecular decoy that competitively inhibits the canonical IL-18Rα1/IL-18Rß signaling pathway. Whereas NK cells and pDCs both express IL-18Rα1, pDCs express significantly higher levels of IL-18Rα2, resulting in differential responses of these populations to IL-18. Flu exposure increases IL-18Rα1 expression in pDCs, and the blocking of IL-18R enhances pDC production of IFN-α and IP-10; thus, pDCs use activation-induced splicing to regulate IFN-α production in response to flu. These data demonstrate that IL-18R modulates IFN-α release by human pDCs and suggest that IL-18R signaling may represent a promising therapeutic target.
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Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Splicing de RNA
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Regulação da Expressão Gênica
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Interferon-alfa
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Receptores de Interleucina-18
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article