IFN-γ stimulates CpG-induced IL-10 production in B cells via p38 and JNK signalling pathways.
Eur J Immunol
; 48(9): 1506-1521, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-30004580
ABSTRACT
The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-γ, a key cytokine in multiple immune processes and pathologies, is known as an inhibitor of IL-10 production by monocytes and macrophages, but also has some regulatory functions. In the present study, we explored the role of IFN-γ on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN-γ inhibited IL-10 production induced by TLR2, TLR3, TLR4 and TLR7/8 agonists, but stimulated IL-10 production when cells were triggered with CpG oligodeoxynucleotides, a specific TLR9 agonist. The stimulatory effect of IFN-γ on TLR9-induced IL-10 was restricted to B cells. In line with the increased IL-10, B cells stimulated with CpG and IFN-γ profoundly inhibited CD4 T cell proliferation. Further research into the mechanisms involved, revealed that the mitogen-activated protein kinases p38 and JNK are essential players in this stimulatory effect, and that the phosphatase MKP1 - an inhibitor of p38 and JNK activity - is downregulated after combined stimulation with IFN-γ and CpG. Our data may represent a novel immunoregulatory role of IFN-γ in B cells after triggering of TLR9, by stimulating IL-10 production.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Interferón gamma
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Interleucina-10
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Islas de CpG
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Proteínas Quinasas JNK Activadas por Mitógenos
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Proteínas Quinasas p38 Activadas por Mitógenos
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Receptor Toll-Like 9
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica