Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis
Kaaij MH, van Tok MN, Blijdorp IC, Ambarus CA, Stock M, Pots D, Knaup VL, Armaka M, Christodoulou-Vafeiadou E, van Melsen TK, Masdar H, Eskes HJ, Yeremenko NG, Kollias G, Schett G, Tas SW, van Duivenvoorde LM, Baeten DL (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 217
Journal Issue: 10
DOI: 10.1084/jem.20200288
Abstract
TNF plays a key role in immune-mediated inflammatory diseases including rheumatoid arthritis (RA) and spondyloarthritis (SpA). It remains incompletely understood how TNF can lead to different disease phenotypes such as destructive peripheral polysynovitis in RA versus axial and peripheral osteoproliferative inflammation in SpA. We observed a marked increase of transmembrane (tm) versus soluble (s) TNF in SpA versus RA together with a decrease in the enzymatic activity of ADAM17. In contrast with the destructive polysynovitis observed in classical TNF overexpression models, mice overexpressing tmTNF developed axial and peripheral joint disease with synovitis, enthesitis, and osteitis. Histological and radiological assessment evidenced marked endochondral new bone formation leading to joint ankylosis over time. SpA-like inflammation, but not osteoproliferation, was dependent on TNF-receptor I and mediated by stromal tmTNF overexpression. Collectively, these data indicate that TNF can drive distinct inflammatory pathologies. We propose that tmTNF is responsible for the key pathological features of SpA.
Authors with CRIS profile
Michael Stock
Department of Medicine 3 – Rheumatology and Immunology
Georg Schett
Lehrstuhl für Innere Medizin III
Involved external institutions
Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra
Netherlands (NL)
Biomedical Sciences Research Center "Alexander Fleming"
Greece (GR)
University of Amsterdam
Netherlands (NL)
Netherlands (NL)
Biomedical Sciences Research Center "Alexander Fleming"
Greece (GR)
University of Amsterdam
Netherlands (NL)
How to cite
APA:
Kaaij, M.H., van Tok, M.N., Blijdorp, I.C., Ambarus, C.A., Stock, M., Pots, D.,... Baeten, D.L. (2020). Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis. Journal of Experimental Medicine, 217(10). https://dx.doi.org/10.1084/jem.20200288
MLA:
Kaaij, Merlijn H., et al. "Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis." Journal of Experimental Medicine 217.10 (2020).
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