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Cambré, Isabelle; Gaublomme, Djoere; Burssens, Arne; Jacques, Peggy; Schryvers, Nadia; De Muynck, Amélie; Meuris, Leander; Lambrecht, Stijn; Carter, Shea; de Bleser, Pieter; Saeys, Yvan; Van Hoorebeke, Luc; Kollias, George; Mack, Matthias; Simoens, Paul; Lories, Rik; Callewaert, Nico; Schett, Georg; Elewaut, Dirk

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

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  • Media type: E-Article
  • Title: Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis
  • Contributor: Cambré, Isabelle; Gaublomme, Djoere; Burssens, Arne; Jacques, Peggy; Schryvers, Nadia; De Muynck, Amélie; Meuris, Leander; Lambrecht, Stijn; Carter, Shea; de Bleser, Pieter; Saeys, Yvan; Van Hoorebeke, Luc; Kollias, George; Mack, Matthias; Simoens, Paul; Lories, Rik; Callewaert, Nico; Schett, Georg; Elewaut, Dirk
  • imprint: Springer Science and Business Media LLC, 2018
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-018-06933-4
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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<jats:italic>CCL2</jats:italic>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.</jats:p>
  • Access State: Open Access