Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis.
Cambre I, Gaublomme D, Burssens A, Jacques P, Schryvers N, De Muynck A, Meuris L, Lambrecht S, Carter S, De Bleser P, Saeys Y, Van Hoorebeke L, Kollias G, Mack M, Simoens P, Lories R, Callewaert N, Schett G, Elewaut D (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 9
Journal Issue: 1
DOI: 10.1038/s41467-018-06933-4
Abstract
Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.
Authors with CRIS profile
Involved external institutions
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Belgium (BE)
Universiteit Gent (UGent) / Ghent University
Belgium (BE)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
VIB-UGent Center for Inflammation Research
Belgium (BE)
Biomedical Sciences Research Center "Alexander Fleming"
Greece (GR)
Universitätsklinikum Regensburg
Germany (DE)
Belgium (BE)
Universiteit Gent (UGent) / Ghent University
Belgium (BE)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
VIB-UGent Center for Inflammation Research
Belgium (BE)
Biomedical Sciences Research Center "Alexander Fleming"
Greece (GR)
Universitätsklinikum Regensburg
Germany (DE)
How to cite
APA:
Cambre, I., Gaublomme, D., Burssens, A., Jacques, P., Schryvers, N., De Muynck, A.,... Elewaut, D. (2018). Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-06933-4
MLA:
Cambre, Isabelle, et al. "Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis." Nature Communications 9.1 (2018).
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