| First Author | Imbrechts M | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 9 | Pages | 1506-1521 |
| PubMed ID | 30004580 | Mgi Jnum | J:265759 |
| Mgi Id | MGI:6200493 | Doi | 10.1002/eji.201847578 |
| Citation | Imbrechts M, et al. (2018) IFN-gamma stimulates CpG-induced IL-10 production in B cells via p38 and JNK signalling pathways. Eur J Immunol 48(9):1506-1521 |
| abstractText | The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-gamma, 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-gamma on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN-gamma 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-gamma on TLR9-induced IL-10 was restricted to B cells. In line with the increased IL-10, B cells stimulated with CpG and IFN-gamma 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-gamma and CpG. Our data may represent a novel immunoregulatory role of IFN-gamma in B cells after triggering of TLR9, by stimulating IL-10 production. |
