O012 Joint-specific synovial TGF-Β1-induced AXL expression determines the outcome of inflammatory arthritis between ankle and knee joints

Introduction Rheumatoid arthritis (RA) manifests in a symmetrical fashion in anatomically distinct synovial joints. The innate immune system, which plays a crucial role in the pathogenesis of RA, is regulated by anti-inflammatory feedback mechanisms such as the tyrosine kinase receptor family TYRO3, AXL and MER. Of importance, AXL is mainly expressed on sentinel cells. Objectives To investigate the synovial expression of AXL and its putative anti-inflammatory role in arthritis. Methods KRN serum transfer arthritis was induced in Axl-/- and wild-type mice. Knee and ankle joints were scored macro- and microscopically. Synovial gene and protein expression of Axl was determined in naive and TGF-β1-overexpressing joints. AXL expression was determined in M1-like or M2-like macrophages and RA synovium. Human macrophages and synovial micromasses were stimulated with TGF-β1 or the AXL inhibitor R428. Results The ankle joints of Axl-/- mice showed an increased macroscopic disease score during arthritis development (p Conclusions Differences in synovial AXL expression are in accordance with the observation that AXL dampens arthritis in ankle, but not in knee joints. We provide evidence that the local differences in AXL expression could be due to TGF-β1, and suggest similar pathways operate in RA synovium. Disclosure of interest None declared