title: Role of interferon regulatory factor 7 in serum-transfer arthritis: regulation of interferon-β production.
abstract: OBJECTIVE
  Innate immune responses activate synoviocytes and recruit inflammatory cells into the rheumatoid joint. Type I interferons (IFNs) play a role in autoimmunity, and IFN gene transcription is activated by IFN-regulatory factors (IRFs) in response to innate sensor recognition. The purpose of this study was to examine the effect of genetic deficiency of IRF-7 in a passive K/BxN serum-transfer model of arthritis.
  
  
  METHODS
  Passive-transfer arthritis was induced in IRF-7(-/-)  mice, and additional groups were treated with IFNβ or poly(I-C). Clinical arthritis scoring, histologic assessment, micro-computed tomography, and synovial tissue quantitative polymerase chain reaction analysis were performed. Mouse serum was analyzed by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  In the passive K/BxN serum-transfer model, arthritis severity was significantly increased in IRF-7(-/-)  mice compared with wild-type (WT) mice. In addition, expression of IFNβ in synovium and serum was decreased, potentially contributing to increased arthritis. IRF-7(-/-)  mice injected with replacement IFNβ had a decrease in arthritis. Poly(I-C) treatment diminished arthritis in IRF-7(-/-)  mice, restored synovial IFNβ gene expression, and increased serum levels of IFNβ. In vitro studies demonstrated that poly(I-C) stimulation of fibroblast-like synoviocytes (FLS) from IRF-7(-/-)  mice resulted in increased induction of proinflammatory gene expression as compared with FLS from WT mice; however, IFNβ expression was not significantly different. In contrast, peritoneal macrophages from IRF-7(-/-)  mice showed significantly less induction of IFNβ in response to poly(I-C) stimulation.
  
  
  CONCLUSIONS
  IRF-7 deficiency exacerbates arthritis and replacement treatment with IFNβ or poly(I-C) decreases arthritis severity. Both macrophage- and synoviocyte-specific roles of IRF-7 likely contribute to the increased arthritis. IRF-7 might play an antiinflammatory role in passive-transfer arthritis through regulation of macrophage IFNβ production.
authors.affiliation: University of California San Diego, La Jolla, CA 92093-0663, USA. ssweeney@ucsd.edu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Sweeney
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Trevor B
authors.initials: TB
authors.lastname: Kimbler
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D002111:Calcaneus / Q000000981:diagnostic imaging; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D011859:Radiography; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta
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