Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial fibroblasts

Olga N Karpus, Kirstin M Heutinck, Paul J M Wijnker, Paul P Tak, Jörg Hamann

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BACKGROUND: CD55 (decay-accelerating factor) is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS). CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS.

METHODS: FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR) ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C)) and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (ds)RNA sensors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I). CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry.

RESULTS: CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C). Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55.

CONCLUSIONS: Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes.

Original languageEnglish
Article numbere35606
Pages (from-to)e35606
Issue number5
Publication statusPublished - 2012


  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD/immunology
  • Arthritis/immunology
  • CD55 Antigens/biosynthesis
  • Cell Communication/drug effects
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases/immunology
  • Female
  • Fibroblasts/immunology
  • Humans
  • Interferon Inducers/pharmacology
  • Interferon-Induced Helicase, IFIH1
  • Interleukin-1beta
  • Leukocytes/immunology
  • Male
  • Middle Aged
  • Poly I-C/pharmacology
  • RNA, Double-Stranded
  • Receptors, G-Protein-Coupled
  • Synovial Membrane/immunology
  • Toll-Like Receptor 3/immunology
  • Up-Regulation

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