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* Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, U.K.;
Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;
Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, U.K.;
Department of Dermatology, School of Medicine, University of California–Davis, Sacramento, CA 95817; and
¶ Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Kragujevac, Republic of Serbia
Galectin-3 (Gal-3) is a member of the β-galactoside-binding lectin family and plays an important role in inflammation. However, the precise role of Gal-3 in autoimmune diseases remains obscure. We have investigated the functional role of Gal-3 in experimental autoimmune encephalomyelitis (EAE) following immunization with myelin oligodendrocyte glycoprotein (MOG)35–55 peptide. Gal-3 deficient (Gal-3–/–) mice developed significantly milder EAE and markedly reduced leukocyte infiltration in the CNS compared with similarly treated wild-type (WT) mice. Gal-3–/– mice also contained fewer monocytes and macrophages but more apoptotic cells in the CNS than did WT mice. Following Ag stimulation in vitro, lymph node cells from the immunized Gal-3–/– mice produced less IL-17 and IFN-
than did those of the WT mice. In contrast, Gal-3–/– mice produced more serum IL-10, IL-5, and IL-13 and contained higher frequency of Foxp3+ regulatory T cells in the CNS than did the WT mice. Furthermore, bone marrow-derived dendritic cells from Gal-3–/– mice produced more IL-10 in response to LPS or bacterial lipoprotein than did WT marrow-derived dendritic cells. Moreover, Gal-3–/– dendritic cells induced Ag-specific T cells to produce more IL-10, IL-5, and IL-12, but less IL-17, than did WT dendritic cells. Taken together, our data demonstrate that Gal-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN- synthesis, but decreasing IL-10 production.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work received financial support from the Medical Research Council and the Wellcome Trust, U.K., and United Arab Emirates University research grant and the Sheikh Hamdan Award for Medical Science, United Arab Emirates.
2 Address correspondence and reprint requests to Dr. F. Y. Liew, Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, 120 University Place, University of Glasgow, Glasgow G12 8TA, U.K. E-mail address: f.y.liew{at}clinmed.gla.ac.uk or Dr. Miodrag L. Lukic, Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia and Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, United Arab Emirates. E-mail address: m.lukic{at}uaeu.ac.ae
3 Abbreviations used in this paper: Gal-3, galectin-3; DLN, draining lymph node; BMDC, bone marrow-derived dendritic cell; EAE, experimental autoimmune encephalomyelitis; iNOS, inducible NO synthase; MOG, myelin oligodendrocyte glycoprotein; Treg, regulatory T; WT, wild-type.
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