Open AccessRole of interferon regulatory factor 7 in serum‐transfer arthritis: Regulation of interferon‐β production
Author(s) -
Sweeney Susan E.,
Corr Maripat,
Kimbler Trevor B.
Publication year - 2012
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.33454
Subject(s) - arthritis , immunology , irf1 , rheumatoid arthritis , proinflammatory cytokine , interferon , medicine , interferon regulatory factors , autoimmunity , immune system , inflammatory arthritis , innate immune system , inflammation , transcription factor , biology , gene , biochemistry
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. Conclusion 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.