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.

Details

Title
Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis
Author
Cambré, Isabelle 1 ; Gaublomme, Djoere 1 ; Burssens, Arne 2 ; Jacques, Peggy 1 ; Schryvers, Nadia 1 ; De Muynck, Amélie 3 ; Meuris, Leander 4   VIAFID ORCID Logo  ; Lambrecht, Stijn 1 ; Carter, Shea 5 ; de Bleser, Pieter 6 ; Saeys, Yvan 6   VIAFID ORCID Logo  ; Luc Van Hoorebeke 3 ; Kollias, George 7 ; Mack, Matthias 8 ; Simoens, Paul 9 ; Lories, Rik 5 ; Callewaert, Nico 4   VIAFID ORCID Logo  ; Schett, Georg 10 ; Elewaut, Dirk 1 

1  Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium; Department of Rheumatology, Ghent University, Ghent University Hospital, Ghent, Belgium 
2  Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium; Department of Rheumatology, Ghent University, Ghent University Hospital, Ghent, Belgium; Department of Orthopaedics and Traumatology, Ghent University Hospital, Ghent, Belgium 
3  UGCT-Department of Physics and Astronomy, Ghent University, Ghent, Belgium 
4  Unit of Medical Biotechnology, VIB Inflammation Research Center (IRC), VIB, Ghent, Belgium; Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium 
5  Department of Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium; Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium 
6  Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium 
7  Division of Immunology, Biomedical Sciences Research Center ‘Alexander Fleming’, Vari, Attica, Greece; Department of Experimental Physiology, School of Medicine, National and Kapodistrian University of Athens, Goudi, Athens, Greece 
8  Deparment of Internal Medicine II – Nephrology, University Hospital Regensburg, Regensburg, Germany 
9  Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium 
10  Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg and Universitatsklinikum, Erlangen, Germany 
Pages
1-14
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06933-4
ProQuest document ID
2130053008
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.