Fisher, Corinne Rhiannon;
(2022)
Investigating the biology of IL23 in monocyte-derived macrophages in enthesitis related arthritis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Enthesitis related arthritis (ERA) is a subtype of juvenile arthritis with many similarities to the adult spondyloarthropathies (SpA). The innate immune system, intracellular stress responses (including the unfolded protein response (UPR)) and IL23/IL17 pathway are implicated in the pathogenesis of adult SpA. However, these systems remain relatively unexplored in ERA. Novel treatments for SpA which inhibit the IL23/IL17 pathway are now available but their role in the treatment of ERA remains unclear. The aim of this thesis was to study the biology of IL23 in the innate immune system (in particular in monocyte-derived macrophages (MDMs)) and other relevant cytokines in patients with ERA, compared to a group of age-matched controls and also adult patients with SpA. A bioassay was developed to produce MDMs which were then stimulated with lipopolysaccharide (LPS). Cytokine production at the protein and RNA level and phosphorylation of p38 MAP kinase were used as outputs for this assay. The effect of induction of the UPR on cytokine production was also studied, as well as a number of serum biomarkers known to be relevant in adult SpA. Key differences were observed in the production of IL23 and other cytokines from LPSstimulated MDMs with higher levels from patients with ERA compared to healthy controls. Enthesitis, HLA B27 and male sex were especially associated with high levels of cytokine production. Induction of the UPR was not associated with increased cytokine production with the exception of GMCSF and there was no evidence of UPR upregulation in patients with ERA or adult SpA. Higher levels of biomarkers including CRP, calprotectin and Dkk1 were observed in patients with ERA compared to healthy controls. The results obtained in this thesis indicate important differences in the biology of IL23 and other cytokines in patients with ERA compared to healthy controls which warrants further study.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the biology of IL23 in monocyte-derived macrophages in enthesitis related arthritis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10161426 |
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