IFN-γ stimulates CpG-induced IL-10 production in B cells via p38 and JNK signalling pathways.

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.

journal_name

Eur J Immunol

authors

Imbrechts M,De Samblancx K,Fierens K,Brisse E,Vandenhaute J,Mitera T,Libert C,Smets I,Goris A,Wouters C,Matthys P

doi

10.1002/eji.201847578

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

1506-1521

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

48

pub_type

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