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

(2018) EUROPEAN JOURNAL OF IMMUNOLOGY. 48(9). p.1506-1521
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Abstract
The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-, 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- on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN- 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- on TLR9-induced IL-10 was restricted to Bcells. In line with the increased IL-10, Bcells stimulated with CpG and IFN- 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- and CpG. Our data may represent a novel immunoregulatory role of IFN- in Bcells after triggering of TLR9, by stimulating IL-10 production.
Keywords
REGULATORY B-CELLS, TOLL-LIKE RECEPTORS, PLASMACYTOID DENDRITIC CELLS, COLLAGEN-INDUCED ARTHRITIS, PROTEIN-KINASE INHIBITORS, CD8(+) T-CELLS, INTERFERON-GAMMA, INTERLEUKIN-10 PRODUCTION, AUTOIMMUNE-DISEASES, VACCINE FAILURE, B cells, interferon-gamma, interleukin-10, mitogen-activated protein, kinases, Toll-like receptor 9

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Citation

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MLA
Imbrechts, Maya, Karen De Samblancx, Karlien Fierens, et al. “IFN-γ Stimulates CpG-induced IL-10 Production in Bcells via P38 and JNK Signalling Pathways.” EUROPEAN JOURNAL OF IMMUNOLOGY 48.9 (2018): 1506–1521. Print.
APA
Imbrechts, M., De Samblancx, K., Fierens, K., Brisse, E., Vandenhaute, J., Mitera, T., Libert, C., et al. (2018). IFN-γ stimulates CpG-induced IL-10 production in Bcells via p38 and JNK signalling pathways. EUROPEAN JOURNAL OF IMMUNOLOGY, 48(9), 1506–1521.
Chicago author-date
Imbrechts, Maya, Karen De Samblancx, Karlien Fierens, Ellen Brisse, Jessica Vandenhaute, Tania Mitera, Claude Libert, et al. 2018. “IFN-γ Stimulates CpG-induced IL-10 Production in Bcells via P38 and JNK Signalling Pathways.” European Journal of Immunology 48 (9): 1506–1521.
Chicago author-date (all authors)
Imbrechts, Maya, Karen De Samblancx, Karlien Fierens, Ellen Brisse, Jessica Vandenhaute, Tania Mitera, Claude Libert, Ide Smets, An Goris, Carine Wouters, and Patrick Matthys. 2018. “IFN-γ Stimulates CpG-induced IL-10 Production in Bcells via P38 and JNK Signalling Pathways.” European Journal of Immunology 48 (9): 1506–1521.
Vancouver
1.
Imbrechts M, De Samblancx K, Fierens K, Brisse E, Vandenhaute J, Mitera T, et al. IFN-γ stimulates CpG-induced IL-10 production in Bcells via p38 and JNK signalling pathways. EUROPEAN JOURNAL OF IMMUNOLOGY. 2018;48(9):1506–21.
IEEE
[1]
M. Imbrechts et al., “IFN-γ stimulates CpG-induced IL-10 production in Bcells via p38 and JNK signalling pathways,” EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 48, no. 9, pp. 1506–1521, 2018.
@article{8583000,
  abstract     = {The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-, 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- on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN- 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- on TLR9-induced IL-10 was restricted to Bcells. In line with the increased IL-10, Bcells stimulated with CpG and IFN- 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- and CpG. Our data may represent a novel immunoregulatory role of IFN- in Bcells after triggering of TLR9, by stimulating IL-10 production.},
  author       = {Imbrechts, Maya and De Samblancx, Karen and Fierens, Karlien and Brisse, Ellen and Vandenhaute, Jessica and Mitera, Tania and Libert, Claude and Smets, Ide and Goris, An and Wouters, Carine and Matthys, Patrick},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keywords     = {REGULATORY B-CELLS,TOLL-LIKE RECEPTORS,PLASMACYTOID DENDRITIC CELLS,COLLAGEN-INDUCED ARTHRITIS,PROTEIN-KINASE INHIBITORS,CD8(+) T-CELLS,INTERFERON-GAMMA,INTERLEUKIN-10 PRODUCTION,AUTOIMMUNE-DISEASES,VACCINE FAILURE,B cells,interferon-gamma,interleukin-10,mitogen-activated protein,kinases,Toll-like receptor 9},
  language     = {eng},
  number       = {9},
  pages        = {1506--1521},
  title        = {IFN-γ stimulates CpG-induced IL-10 production in Bcells via p38 and JNK signalling pathways},
  url          = {http://dx.doi.org/10.1002/eji.201847578},
  volume       = {48},
  year         = {2018},
}

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