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AB0176 increased toll-like receptor 5 signalling and IL-6 production in monocytes from patients with systemic lupus erythematosus
journal contribution
posted on 2023-06-09, 05:23 authored by Kevin DaviesKevin Davies, R Thwaites, P Emery, F Ponchel, Sandra SacreSandra SacreBackground The innate immune system contributes to the pathogenesis of SLE, in part through the activity of Toll-like receptors (TLRs), a family of pattern-recognition receptors. Nucleic acid containing immune-complexes, which are characteristic of SLE, activate the RNA and DNA sensing TLRs 7 and 9, resulting in interferon production [1]. Although a role for interferon is well established in SLE, other cytokines such as interleukin (IL)-6 have also been shown to correlate with disease activity, with an anti-IL-6 receptor antibody (Tocilizumab) demonstrating some early success in clinical trials [2][3]. Objectives TLR-7 and 9 are primarily considered drivers of IFN production, but in this study, our aim was to explore the biology of other key TLR's (4, 5 and 8) in SLE in vitro, specifically the role of these TLR's in the induction of interleukin-6 production by monocytes. Methods Freshly-obtained peripheral blood monocytes from patients with known SLE (satisfying standard diagnostic and seroplogical criteria) were studied, contemporaneously with cells from healthy volunteers. TLR expression was evaluated by flow cytometry. Monocyte IL-6 production was measured by ELISA, and evaluation of mRNA levels, before and after in vitro stimulation with flagellin. Results An increase in TLR5 expression (p<0.001; 30 patients and controls) and TLR5-induced IL-6 production was observed in SLE monocytes: (HC mean 0.311ng/ml; SLE mean 2.26ng/ml), p=0.0447; 31 patients, 19 controls). Additionally, downstream regulators of TLR5 signalling were also found to be dysregulated at the mRNA level in the patient samples, showing a direct correlation with TLR5 induced IL-6 production (p=0.0005, r2=0.515). Conclusions These data suggest that there is altered expression and function of TLR5 in SLE patient monocytes. Our results indicate that this may be a factor contributing to incresaed IL-6 levels in the paient group, with potential pathogenic implications. With further charactertisation this pathway may be amenable to therapeutic modification in the future.
History
Publication status
- Published
Journal
Annals of the Rheumatic DiseasesISSN
0003-4967Publisher
BMJ Publishing GroupIssue
2Volume
74Article number
a949Event type
conferenceDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2017-03-06Usage metrics
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