The level of synovial AXL expression determines the outcome of inflammatory arthritis, possibly depending on the upstream role of TGF-β1.
In: Rheumatology (Oxford, England), Jg. 58 (2019-03-01), Heft 3, S. 536-546
Online
academicJournal
Zugriff:
Objective: To investigate the role of AXL, a member of the anti-inflammatory TYRO3, AXL MER (TAM) receptor family, 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 naïve and TGF-β1-overexpressing joints. AXL expression was determined in M1-like or M2-like macrophages and RA synovium. Human macrophages, fibroblasts and synovial micromasses were stimulated with TGF-β1 or the AXL inhibitor R428.
Results: Ankle joints of Axl-/- mice showed exacerbated arthritis pathology, whereas no effect of Axl gene deletion was observed on gonarthritis pathology. To explain this spatial difference, we examined the synovium of naïve mice. In contrast to the knee, the ankle synovial cells prominently expressed AXL. Moreover, the M2-like macrophage phenotype was the dominant cell type in the naïve ankle joint. Human M2-like macrophages expressed higher levels of AXL and blocking AXL increased their inflammatory response. In the murine ankle synovium, gene expression of Tgfb1 was increased and Tgb1 correlated with Axl. Moreover, TGFB1 and AXL expression also correlated in human RA synovium. In human macrophages and synovial micromasses, TGF-β1 enhanced AXL expression. Moreover, TGF-β1 overexpression in naïve murine knee joints induced synovial AXL expression.
Conclusion: 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.
(© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
| Titel: |
The level of synovial AXL expression determines the outcome of inflammatory arthritis, possibly depending on the upstream role of TGF-β1.
|
|---|---|
| Autor/in / Beteiligte Person: | Waterborg, CEJ ; Broeren, MGA ; Blaney Davidson, EN ; Koenders, MI ; van Lent PLEM ; van den Berg WB ; van der Kraan PM ; van de Loo FAJ |
| Link: | |
| Zeitschrift: | Rheumatology (Oxford, England), Jg. 58 (2019-03-01), Heft 3, S. 536-546 |
| Veröffentlichung: | Oxford, UK : Avenel, N.J. : Oxford University Press ; Distributed by Mercury International, c1999-, 2019 |
| Medientyp: | academicJournal |
| ISSN: | 1462-0332 (electronic) |
| DOI: | 10.1093/rheumatology/key337 |
| Schlagwort: |
|
| Sonstiges: |
|