Rheumatoide Arthritis - T-Zell-unabhängige Mechanismen

Zusammenfassung

Die rheumatoide Arthritis (RA) ist eine chronisch entzündliche Systemerkrankung, manifestiert sich allerdings vor allem an den Gelenken. Sie führt bei vielen Patienten zu einer progressiven Destruktion artikulärer Strukturen, die durch das invasive Einwachsen der hyperplastischen Synovialmembran in den Knorpel und Knochen verursacht wird. Neben Entzündungs- und Immunzellen spielen Fibroblasten eine wichtige Rolle in der Pathogenese der Erkrankung. So sind diese Zellen über ihre Anheftung an den Knorpel und die Produktion matrixzerstörender Enzyme ganz entscheidend am Destruktionsprozess beteiligt. Neuere Untersuchungen belegen zudem eine wichtige Rolle der Fibroblasten bei der Rekrutierung von Entzündungszellen und der Chronifizierung der rheumatoiden Synovitis. Verschiedene Untersuchungen zeigen, dass synoviale Fibroblasten bei RA eine stabile Aktivierung aufweisen, die auch unabhängig vom Entzündungsgeschehen aufrechterhalten wird. Diese führt in einem sich zum Teil selbst unterhaltenden Prozess zur Expression von Adhäsionsmolekülen und matrixabbauenden Enzymen sowie zu Veränderungen im programmierten Zelltod. Diese zentralen Eigenschaften synovialer Fibroblasten bei RA stehen daher im Zentrum aktueller Forschungen zur Pathogenese und stellen potenzielle Angriffspunkte für neue therapeutische Ansätze dar.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that shows systemic involvement but primarily affects the joints. In many patients, it results in the progressive destruction of articular structures, caused by invasive growth of the hyperplastic synovial membrane into cartilage and bone. Apart from inflammatory and immune cells, synovial fibroblasts play an important role in the pathogenesis of the disease. These cells are significantly involved in the destructive process through their adhesion to cartilage and the production of matrix-degrading enzymes. Recent data also point to an important role of fibroblasts in the recruitment of inflammatory cells and the chronification of rheumatoid synovitis. A number of studies have demonstrated that RA synovial fibroblasts exhibit features of stable cellular activation that is maintained with or without synovial inflammation. In a self-perpetuating manner, this activation results in the expression of adhesion molecules and matrix-degrading enzymes as well as in alterations in programmed cell death. Current research on the pathogenesis of RA focuses on these central features of RA synovial fibroblasts, thus constituting potential targets for novel therapeutic approaches.

Schlüsselwörter

Apoptose - Fibroblasten - Rheumatoide Arthritis

Key words

Apoptosis - fibroblasts - rheumatoid arthritis

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