title: The roles of Galectin-3 in autoimmunity and tumor progression.
abstract: Galectin-3, a unique chimera-type member of the β-galactoside-binding soluble lectin family, is widely expressed in numerous cells. Here, we discuss the role of Galectin-3 in T-cell-mediated inflammatory (auto) immunity and tumor rejection by using Galectin-3-deficient mice and four disease models of human pathology: experimental autoimmune encephalomyelitis (EAE), Con-A-induced hepatitis, multiple low-dose streptozotocin-induced diabetes (MLD-STZ diabetes) and metastatic melanoma. We present evidence which suggest that Galectin-3 plays an important pro-inflammatory role in Con-A-induced hepatitis by promoting the activation of T lymphocytes, NKT cells and DCs, cytokine secretion, prevention of M2 macrophage polarization and apoptosis of mononuclear cells, and it leads to severe liver injury. In addition, experiments in Galectin-3-"knock-out" mice indicate that Galectin-3 is also involved in immune-mediated β-cell damage and is required for diabetogenesis in MLD-STZ model by promoting the expression of IFN-gamma, TNF-alpha, IL-17 and iNOS in immune and accessory effector cells. Next, our data demonstrated that Galectin-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10 production. Finally, based on our findings, we postulated that expression of Galectin-3 in the host may also facilitate melanoma metastasis by affecting tumor cell adhesion and modulating anti-melanoma immune response, in particular innate antitumor immunity. Taken together, we discuss the evidence of pro-inflammatory and antitumor activities of Galectin-3 and suggest that Galectin-3 may be an important therapeutic target.
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Radosavljevic
authors.forename: Vladislav
authors.initials: V
authors.lastname: Volarevic
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanovic
authors.forename: Marija
authors.initials: M
authors.lastname: Milovanovic
authors.forename: Nada
authors.initials: N
authors.lastname: Pejnovic
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hsu
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
mesh_terms: D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006505:Hepatitis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D037502:Galectin 3