IL17RD is a member of the IL17 receptor family. In contrast to the other IL17 receptors, IL17RA, -RB, -RC and -RE, little is known about the ligand and function of IL17RD. Recently, IL17RD has been described to negatively regulate a selection of IL17A responsive genes. IL17RD is therefore proposed to limit IL17A signalling. In this study we examined how IL17RD expression could be regulated and whether a reduction of IL17RD contributes to the development of Rheumatoid Arthritis.Materials and Methods
Human synovial fibroblasts from Rheumatoid Arthritis (RA) patients were stimulated with tumour necrosis factor α (TNFα), interleukin 1 β (IL1β) or IL17A for 4 and 24 hours. Human synovial fibroblasts were further stimulated with TNFα for 48 and 72 hours. IL17RD expression levels were measured via qPCR. Collagen induced arthritis (CIA) was induced in IL17RD 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.Results
Human synovial fibroblasts from RA patients have baseline expression of IL17RD. Upon stimulation with TNFα a significant downregulation of IL17RD expression was measured from 24 hours onwards. IL1β stimulation had a similar effect as TNFα on IL17RD expression, resulting in a significant downregulation at 4 and 24 hours. Lack of IL-17RD did not result in differences in CIA severity, but preliminary data suggest changes in the incidence between IL-17RD knockout mice compared to wild type littermates.Conclusions
An inflammatory environment causes synovial fibroblasts to downregulate IL17RD expression. Lack of IL17RD did not influence the severity of CIA.