Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis

Isabelle Cambré, Djoere Gaublomme, Arne Burssens, Peggy Jacques, Nadia Schryvers, Amélie Muynck, Leander Meuris, Stijn Lambrecht, Shea Carter, Pieter Bleser, Yvan Saeys, Luc Hoorebeke, George Kollias, Matthias Mack, Paul Simoens, Rik Lories, Nico Callewaert, Georg Schett and Dirk Elewaut ()
Additional contact information
Isabelle Cambré: VIB Inflammation Research Center (IRC)
Djoere Gaublomme: VIB Inflammation Research Center (IRC)
Arne Burssens: VIB Inflammation Research Center (IRC)
Peggy Jacques: VIB Inflammation Research Center (IRC)
Nadia Schryvers: VIB Inflammation Research Center (IRC)
Amélie Muynck: Ghent University
Leander Meuris: VIB Inflammation Research Center (IRC), VIB
Stijn Lambrecht: VIB Inflammation Research Center (IRC)
Shea Carter: KU Leuven
Pieter Bleser: VIB Center for Inflammation Research
Yvan Saeys: VIB Center for Inflammation Research
Luc Hoorebeke: Ghent University
George Kollias: Biomedical Sciences Research Center ‘Alexander Fleming’
Matthias Mack: University Hospital Regensburg
Paul Simoens: Ghent University
Rik Lories: KU Leuven
Nico Callewaert: VIB Inflammation Research Center (IRC), VIB
Georg Schett: Friedrich Alexander University of Erlangen-Nuremberg and Universitatsklinikum
Dirk Elewaut: VIB Inflammation Research Center (IRC)

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06933-4

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