CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis

Abstract

Introduction: CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. Methods: Synovial tissue, primary FLS cultures, and three-dimensional FLS micromasses were analyzed. CD55 expression was assessed by quantitative polymerase chain reaction (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular fibers were visualized by Gomori staining and colocalization of CD55 with extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55 was released from synovial tissue with phospholipase C. Functional consequences of CD55 expression were studied in the K/BxN serum transfer model of arthritis using mice that in addition to CD55 also lack FcγRIIB (CD32), increasing susceptibility for immune complex-mediated pathology. Results: Abundant CD55 expression seen in FLS of the intimal lining layer was associated with linearly oriented reticular fibers and was resistant to phospholipase C treatment. Expression of CD55 colocalized with collagen type I and III as well as with complement C3. A comparable distribution of CD55 was established in three-dimensional micromasses after ≥3 weeks of culture together with the ECM. CD55 deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated disease activity in Fcgr2b -/- mice. Conclusions: CD55 is produced by FLS and deposited on the local collagen fiber meshwork, where it protects the synovial tissue against immune complex-mediated arthritis.