title: Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial fibroblasts.
abstract: 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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Karpus
authors.forename: Kirstin M
authors.initials: KM
authors.lastname: Heutinck
authors.forename: Paul J M
authors.initials: PJ
authors.lastname: Wijnker
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001168:Arthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018958:CD55 Antigens / Q000096:biosynthesis* / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D000072640:Interferon-Induced Helicase, IFIH1; D053583:Interleukin-1beta; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D018958:CD55 Antigens; C508585:IL1B protein, human; D007369:Interferon Inducers; D053583:Interleukin-1beta; D012330:RNA, Double-Stranded; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C