Zusammenfassung
Die rheumatoide Arthritis (RA) ist eine Autoimmunerkrankung und gekennzeichnet durch Synovitis, synoviale Hyperplasie sowie durch eine fortschreitende Zerstörung der betroffenen Gelenke. An diesen Prozessen sind neben den Zellen des Immunsystems auch die synovialen Fibroblasten (RASF) aus der Gelenkinnenhaut maßgeblich beteiligt. Diese pathogenen RASF weisen einen deutlich aktivierten Phänotyp auf: Durch die veränderte Expression von Adhäsionsmolekülen sind sie in der Lage, an den Gelenkknorpel zu adhärieren und diesen durch die Sekretion verschiedener Proteasen aktiv zu zerstören. Des Weiteren tragen sie durch die Ausschüttung verschiedener Zytokine und Chemokine zur Aufrechterhaltung der anhaltenden Entzündungsreaktion bei. Die Ergebnisse der letzten Jahre verdeutlichen, dass RASF nicht nur passiv auf das proinflammatorische Milieu in den entzündeten Gelenken von RA-Patienten reagieren, sondern dieses auch durch die Freisetzung verschiedener Zytokine und Chemokine aktiv verändern. Diese proinflammatorischen Zytokine begünstigen hierbei die Transformation von RASF in einen aggressiven und invasiven Phänotyp. Darüber hinaus tragen die primär veränderten RASF auch selbst aktiv zur Rekrutierung und Aktivierung von immunologisch relevanten Zellen bei. Aufgrund dieser Eigenschaften übernehmen sie eine zentrale Rolle in der Ausbildung und Chronifizierung der destruktiven Entzündungsreaktion in den von RA betroffenen Gelenken.
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis, synovial hyperplasia and progressive degeneration of affected joints. These processes are mediated by cells of the immune system as well as by synovial fibroblasts (RASF) originating from the lining layer of the synovium. In this scenario RASFs display an activated phenotype: they show an altered expression of adhesion molecules which allows attachment to articular cartilage and by synthesis of proteases they mediate progressive cartilage and bone destruction. Furthermore, they produce various cytokines and chemokines, which are essential for promoting the inflammatory response. In recent years it has become evident that RASFs not only passively respond to the proinflammatory milieu in the joints of RA patients but also actively contribute by the overproduction of several cytokines and chemokines. These proinflammatory cytokines trigger the transformation of RASFs into an aggressive and invasive phenotype. Additionally, the primarily altered genuine RASFs are actively involved in the recruitment and activation of immune cells. Taken together, they are key players in the development of the well-known chronic, destructive inflammatory response in joints affected by RA.
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Interessenkonflikt. C. Schönfeld, T. Pap, E. Neumann und U. Müller-Ladner geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Schönfeld, C., Pap, T., Neumann, E. et al. Fibroblasten als pathogene Zellen in der rheumatischen Entzündung. Z. Rheumatol. 74, 33–38 (2015). https://doi.org/10.1007/s00393-014-1439-3
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DOI: https://doi.org/10.1007/s00393-014-1439-3