Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis.

Autor:	Kaaij MH; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., van Tok MN; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Blijdorp IC; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Ambarus CA; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Stock M; Medizinische Klinik 3 - Rheumatologie und Immunologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Pots D; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Knaup VL; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Armaka M; Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming,' Vari, Greece.; Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Christodoulou-Vafeiadou E; Biomedcode Hellas Société Anonyme, Vari, Greece., van Melsen TK; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Masdar H; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Eskes HJPP; Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Yeremenko NG; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Kollias G; Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming,' Vari, Greece.; Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Schett G; Medizinische Klinik 3 - Rheumatologie und Immunologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Tas SW; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., van Duivenvoorde LM; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Baeten DLP; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2020 Oct 05; Vol. 217 (10).
DOI:	10.1084/jem.20200288
Abstrakt:	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. Competing Interests: Disclosures: G. Kollias reported personal fees from Biomedcode Hellas SA outside the submitted work. D.L.P. Baeten reported other from UCB outside the submitted work; and has been an employee of UCB since August 2016. The work described in this paper was conducted in D.L.P. Baeten's lab before he joined UCB, and the work has no relationship at all with his current professional activities at UCB. No other disclosures were reported. (© 2020 Kaaij et al.)
Databáze:	MEDLINE
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