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Title: Systemic juvenile idiopathic arthritis-like syndrome in mice following stimulation of the immune system with complete Freund's adjuvant: Regulation by IFN- γ
Authors: Avau, Anneleen
Mitera, Tania
Put, St├ęphanie
Put, Karen
Brisse, Ellen
Filtjens, Jessica
Uyttenhove, Catherine
Van Snick, Jacques
Liston, Adrian
Leclercq, Georges
Billiau, An D
Wouters, Carine
Matthys, Patrick # ×
Issue Date: May-2014
Publisher: Wiley
Series Title: Arthritis & Rheumatology vol:66 pages:1340-1351
Article number: 10.1002/art.38359
Abstract: Objective Systemic juvenile idiopathic arthritis (sJIA) is unique among rheumatic diseases of childhood, given its distinctive systemic inflammatory character. Inappropriate control of innate immune responses following an initially harmless trigger is thought to account for the excessive inflammatory reaction in patients. We aimed to generate a similar systemic inflammatory syndrome in mice by injection of a relatively innocuous, yet persistent trigger of the immune system: complete Freund's adjuvant (CFA), containing heat-killed mycobacteria. Methods Given the central role of IFN-γ in immune regulation, wild-type and IFN-γ-deficient (IFN-γ KO) BALB/c mice were challenged with CFA. Clinical symptoms and biological characteristics were analyzed. Production of cytokines was examined and effects of anti-cytokine antibodies were investigated. Results In wild-type mice, CFA injection resulted in splenomegaly, lymphadenopathy, neutrophilia, thrombocytosis and increased cytokine expression. In the absence of IFN-γ, symptoms were more pronounced and accompanied by weight loss, arthritis, anemia, hemophagocytosis, abundance of immature blood cells and increased IL-6, all reminiscent of symptoms in sJIA. CFA-challenged IFN-γ KO mice showed increased expression of IL-17 by CD4(+) T cells and by the innate γδ T cells. Inflammatory and hematological changes were prevented by anti-IL-12/IL-23p40 and anti-IL-17 antibodies. Conclusion CFA-immune stimulation in IFN-γ KO mice produces a systemic inflammatory syndrome reflecting the clinical, biological and histopathological picture of sJIA. The protective function of IFN-γ in preventing anemia and overall systemic inflammation is a striking observation. The finding that both adaptive and innate T cells are important sources of IL-17 may be of relevance in the pathogenesis of sJIA. © 2013 American College of Rheumatology.
ISSN: 2326-5205
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Pediatric Immunology
Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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