| Autor: |
Cambré, 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. |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Popis: |
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. © 2018, The Author(s). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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