SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7.
J Immunol
; 194(10): 4737-49, 2015 May 15.
Article
en En
| MEDLINE
| ID: mdl-25862818
ABSTRACT
Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both ß-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Interferón Tipo I
/
Factor 7 Regulador del Interferón
/
Receptor Toll-Like 9
/
Proteínas de Membrana de los Lisosomas
/
Receptores Depuradores
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article