Drs. Forsman and Islander contributed equally to this work.
Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis
Article first published online: 28 JAN 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 2, pages 445–454, February 2011
How to Cite
Forsman, H., Islander, U., Andréasson, E., Andersson, A., Önnheim, K., Karlström, A., Sävman, K., Magnusson, M., Brown, K. L. and Karlsson, A. (2011), Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis & Rheumatism, 63: 445–454. doi: 10.1002/art.30118
- Issue published online: 28 JAN 2011
- Article first published online: 28 JAN 2011
- Accepted manuscript online: 27 OCT 2010 02:53PM EST
- Manuscript Accepted: 21 OCT 2010
- Manuscript Received: 7 APR 2010
- Swedish Society for Medicine
- Swedish Medical Research Council
- Inga Lisa and Arne Lundberg Foundation
- King Gustaf V Memorial Foundation
- Swedish government under the agreement about medical research (ALF)
- European Union Seventh Framework Programme. Grant Number: FP7/2007-2013 grant 221094
Galectin 3, an endogenous β-galactoside–binding lectin, plays an important role in the modulation of immune responses. The finding that galectin 3 is present in the inflamed synovium in patients with rheumatoid arthritis suggests that the protein is associated with the pathogenesis of this disease. We undertook this study to investigate the influence of galectin 3 deficiency in a murine model of arthritis.
Wild-type (WT) and galectin 3–deficient (galectin 3−/−) mice were subjected to antigen-induced arthritis (AIA) through immunization with methylated bovine serum albumin. The concentration of serum cytokines (interleukin-6 [IL-6] and tumor necrosis factor α [TNFα]) and antigen-specific antibodies was evaluated using a cytometric bead array platform and enzyme-linked immunosorbent assay (ELISA). Cellular IL-17 responses were examined by flow cytometry, ELISA, and enzyme-linked immunospot assay.
The joint inflammation and bone erosion of AIA were markedly suppressed in galectin 3−/− mice as compared with WT mice. The reduced arthritis in galectin 3−/− mice was accompanied by decreased levels of antigen-specific IgG and proinflammatory cytokines. The frequency of IL-17–producing cells in the spleen was reduced in galectin 3−/− mice as compared with WT mice. Exogenously added recombinant galectin 3 could partially restore the reduced arthritis and cytokines in galectin 3−/− mice.
Our findings show that galectin 3 plays a pathogenic role in the development and progression of AIA and that the disease severity is accompanied by alterations of antigen-specific IgG levels, systemic levels of TNFα and IL-6, and frequency of IL-17–producing T cells. To our knowledge, this is the first report of in vivo evidence that galectin 3 plays a crucial role in the development of arthritis.