title: Development of proteoglycan-induced arthritis is critically dependent on Fcgamma receptor type III expression.
abstract: OBJECTIVE
  To study the necessity for activating Fcgamma receptor types I and III (FcgammaRI and FcgammaRIII) in proteoglycan-induced arthritis (PGIA), a murine model of rheumatoid arthritis, and to determine whether usage of FcgammaRI or FcgammaRIII correlates with the Th1 phenotype or the autoantibody isotype in PGIA.
  
  
  METHODS
  PGIA was induced by immunizing FcgammaRI(-/-), FcgammaRIII(-/-), and wild-type (WT) littermate mice with human PG. The development and severity of arthritis were monitored over time. PG-specific T cell interleukin-2 (IL-2) production and B cell antibody responses were assessed. FcgammaRIII blocking antibodies were used to inhibit arthritis in an adoptive transfer system. Inflammation in the hind paws was evaluated by assessing cytokine and chemokine messenger RNA (mRNA) transcripts by real-time polymerase chain reaction.
  
  
  RESULTS
  FcgammaRI(-/-) mice developed arthritis with similar kinetics and severity as WT littermate controls, whereas FcgammaRIII(-/-) mice failed to develop the disease. Both FcgammaRI(-/-) and FcgammaRIII(-/-) mice produced similar amounts of PG-specific antibody and IL-2 as littermate controls. Transfer of arthritis was successfully blocked in mice treated with a blocking antibody against FcgammaRIII. FcgammaRIII(-/-) mice displayed a significant decrease in cytokine and chemokine mRNA transcripts obtained from the hind paws of immunized mice, whereas FcgammaRI(-/-) mice demonstrated a similar increase in cytokine and chemokine transcripts as controls.
  
  
  CONCLUSIONS
  These results demonstrate that FcgammaRIII expression is critical to the development of PGIA, and usage of FcgammaRIII correlates with the IgG1 isotype of the PG-specific antibody response. FcgammaRIII expression appears to be important in the effector phase of arthritis, possibly by activating cytokine- and chemokine-secreting cells in the joint.
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Kaplan
authors.forename: Yancia
authors.initials: Y
authors.lastname: Cao
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Miklos
authors.initials: M
authors.lastname: Tunyogi-Csapo
authors.forename: Alison
authors.initials: A
authors.lastname: Finnegan
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D011509:Proteoglycans; D012333:RNA, Messenger; D017452:Receptors, IgG