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Title: Protective role of IFN-{gamma} in collagen-induced arthritis conferred by inhibition of mycobacteria-induced granulocyte chemotactic protein-2 (GCP-2) production
Authors: Kelchtermans, Hilde ×
Struyf, Sofie
De Klerck, Bert
Mitera, Tania
Alen, Marijke
Geboes, Lies
Van Balen, Maarten
Dillen, Christiane
Put, Willy
Gysemans, Conny
Billiau, Alfons
Van Damme, Jozef
Matthys, Patrick #
Issue Date: Apr-2007
Publisher: Liss
Series Title: Journal of Leukocyte Biology vol:81 issue:4 pages:1044-1053
Abstract: Mice with a disrupted IFN-gamma system are remarkably susceptible to experimental autoimmune diseases, such as collagen-induced arthritis (CIA), which rely on the use of CFA. The inflammatory lesions of these IFN-gamma knockout (KO) mice are characterized by an excessive proportion of neutrophils. Here, we show that the increased severity of CIA in IFN-gammaR KO as compared with wild-type mice is accompanied by increased levels of the CXC chemokine granulocyte chemotactic protein-2 (GCP-2), a major neutrophil-attracting chemokine in mice. We demonstrated that the heat-killed mycobacteria present in CFA elicited production of GCP-2 in mouse embryo fibroblast cultures and that this production was inhibited by IFN-gamma. Inhibition of GCP-2 production by IFN-gamma was STAT-1-dependent. IFN-gamma receptor KO mice treated with neutralizing anti-GCP-2 antibodies were protected from CIA, indicating the in vivo importance of GCP-2 in the pathogenesis of CIA. Our data support the notion that one of the mechanisms whereby endogenous IFN-gamma mitigates the manifestations of CIA consists of inhibiting production of GCP-2, thereby limiting mobilization and infiltration of neutrophils, which are important actors in joint inflammation. These results may also be applicable to other experimental models of autoimmunity that rely on the use of CFA.
ISSN: 0741-5400
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Laboratory of Molecular Immunology (Rega Institute)
Laboratory of Virology and Chemotherapy (Rega Institute)
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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