1. Galectin-3 Deficiency Reduces the Severity of Experimental Autoimmune Encephalomyelitis
- Author
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Carl S. Goodyear, Sandra Y. Fukada, Fu-Tong Liu, Zakeya Al Rasebi, Hui-Rong Jiang, Allen Shahin, Damo Xu, Miodrag L. Lukic, E. P. K. Mensah-Brown, and Foo Y. Liew
- Subjects
Central Nervous System ,Male ,Encephalomyelitis, Autoimmune, Experimental ,Galectin 3 ,Encephalomyelitis ,Immunology ,Down-Regulation ,Apoptosis ,Mice, Transgenic ,Inflammation ,Biology ,Severity of Illness Index ,Myelin oligodendrocyte glycoprotein ,Mice ,medicine ,Animals ,Immunology and Allergy ,Lymph node ,Cells, Cultured ,Glycoproteins ,Mice, Knockout ,Interleukin-17 ,Experimental autoimmune encephalomyelitis ,FOXP3 ,medicine.disease ,Growth Inhibitors ,Peptide Fragments ,Interleukin-10 ,Up-Regulation ,Mice, Inbred C57BL ,Interleukin 10 ,medicine.anatomical_structure ,biology.protein ,Myelin-Oligodendrocyte Glycoprotein ,medicine.symptom - Abstract
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-γ 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-γ synthesis, but decreasing IL-10 production.
- Published
- 2009