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

European Journal of Immunology
Maya ImbrechtsPatrick Matthys

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...Continue Reading

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Citations

Sep 30, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maya ImbrechtsPatrick Matthys
Dec 22, 2020·Immunological Reviews·Siyuan MaMübeccel Akdis
Nov 7, 2019·Seminars in Immunology·Catia CerqueiraSimon Fillatreau
Jun 15, 2021·Frontiers in Immunology·Ide SmetsAn Goris

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