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- W2326439752 abstract "Background and objectives GM-CSF is a pro-inflammatory cytokine suggested to be mainly expressed by the Th17 cell subset. Combination blocking of GM-CSF and the key Th17-cytokine IL-17 has shown to be much more effective in reducing experimental arthritis compared to single cytokine blocking, revealing a potential connexion between the two cytokines. With this study, we aimed to unravel the interplay between GM-CSF and IL-17 during Th17 differentiation ex vivo and in vivo during experimental arthritis. Materials and methods We investigated whether IL-17 and GM-CSF levels were affected in a similar fashion when differentiating naive murine CD4 + T cells ex vivo under conditions suboptimal for Th17 development. Additionally, we determined the effect of incubation with GM-CSF and IL-17 recombinant proteins and neutralising antibodies on expression of both cytokines during ex vivo Th17 differentiation. Finally, we studied the IL-17/GM-CSF interplay in C57Bl6/J mice with mBSA/IL-1β-induced experimental arthritis treated with anti-GM-CSF or anti-IL-17 antibodies. Results Interestingly, our ex vivo studies showed increased GM-CSF levels after differentiating naive cells under conditions suboptimal for Th17 development, while IL-17 levels decreased as expected. In line with this ex vivo finding, we observed higher systemic levels of IL-17 and GM-CSF in mice with experimental arthritis after GM-CSF and IL-17 neutralisation respectively. Remarkably, no effects of incubation of naive CD4 + T cells with IL-17 or GM-CSF recombinant proteins or neutralising antibodies during T cell differentiation were detected. This indicates that the two cytokines do not directly regulate each other’s expression but require interaction with environmental cells for their suppressive actions. Conclusion These data point towards deviating differentiation conditions and indirect antagonistic regulation of IL-17 and GM-CSF expression by CD4 + T cells, and provides further rationale for a combination blocking strategy of IL-17 and GM-CSF in treatment of Rheumatoid Arthritis." @default.
- W2326439752 created "2016-06-24" @default.
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- W2326439752 date "2016-02-01" @default.
- W2326439752 modified "2023-09-26" @default.
- W2326439752 title "A2.07 Antagonisticregulation of IL-17 and GM-CSF during cell developmentex vivoand during experimental arthritis" @default.
- W2326439752 doi "https://doi.org/10.1136/annrheumdis-2016-209124.42" @default.
- W2326439752 hasPublicationYear "2016" @default.
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