THU0086 Interleukin 17 receptor d (IL-17RD) reduces incidence of collagen induced arthritis. (12th June 2018)

• Record Type: Journal Article
• Authors: Molendijk, M.; Mus, A.M.; Asmawidjaja, P.S.; Baeten, D.; Lubberts, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 266
• Page End: 266
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.7117
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: IL-17RD is a member of the IL-17 receptor family. In contrast to the other IL-17 receptors, IL-17RA, -RB, -RC and -RE, little is known about the ligand and function of IL-17RD. Recently, IL-17RD has been described to negatively regulate a selection of IL-17A responsive genes. IL-17RD is therefore proposed to limit IL-17A signalling. Objectives: In this study we examined IL-17RD expression in multiple cells types and its role in the development of collagen induced arthritis. Methods: Human synovial fibroblasts from Rheumatoid Arthritis (RA) patients were stimulated with tumour necrosis factor α (TNFα), interleukin 1 β (IL-1β) or IL-17A for multiple time points. IL-17RD expression levels were measured via qPCR. Collagen induced arthritis (CIA) was induced in IL-17RD knockout mice and wildtype littermates. At days 1 and 21, mice were immunised intradermally with chicken collagen type II in complete Freund's adjuvant (CFA). Mice were scored 3 times a week for clinical disease defined as swollen joints with a maximum score of 8. Due to ethical reasons, mice were removed from the experiments when they reached a score of 6. CD4 + memory T cells, CD8 + memory T cells, CD19 + B cells and monocytes were isolated from WT spleens and analysed for IL-17RD expression. Blood neutrophil migration assays were performed in vitro using WT and IL-17RD deficient (IL-17RD KO) mouse synovial fibroblasts. Results: Human synovial fibroblasts from RA patients have baseline expression of IL-17RD. Upon stimulation with TNFα a significant downregulation of IL-17RD expression was measured from 24 hours onwards. IL1β stimulation had a similar effect as TNFα on IL-17RD expression. Lack of IL-17RD did not result in differences in CIA severity, but the incidence of CIA was reduced. IL-17RD is mainly expressed in synovial fibroblasts. IL-17RD KO synovial fibroblasts attract less neutrophils likely by lower production of neutrophil attractants. Conclusions: An inflammatory environment causes synovial fibroblasts to downregulate IL-17RD expression. Lack of IL-17RD reduces the incidence CIA, which is an IL-17-driven model. The decrease in CIA incidence is likely explained via the reduced attraction of neutrophils to the site of inflammation. Disclosure of Interest: None declared