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Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice

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Abstract

Experimental autoimmune myocarditis (EAM) is a mouse model of immune-mediated myocarditis and cardiomyopathy. The role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in autoimmune myocarditis has not been studied. Therefore, the aim of this study was to delineate the role of Gal-3 in myosin peptide-induced autoimmune myocarditis in mice. EAM was induced in relatively resistant C57BL/6J mice (wild type, WT) and in mice with a targeted deletion of Gal-3 gene (Gal-3KO) by immunization with myosin peptide MyHCα334–352. Gal-3KO mice developed more severe myocarditis and more pronounced heart hypertrophy than WT mice. Increased infiltration of CD45+ leucocytes, CD3+ T cells, F4/80+ macrophages, and eosinophils was observed in hearts of Gal-3KO mice compared to WT mice on day 21 after EAM induction. Moreover, hearts of Gal-3KO mice had more T helper type 2 (Th2) cells, alternatively activated M2 macrophages, higher amounts of IgG deposits, and higher serum levels of IL-4 and IL-33 than WT mice. Ablation of Gal-3 in Th1-dominant C57BL/6J mice that are relatively resistant to EAM resulted in more severe disease characterized by type 2 cardiac inflammation. The complex effects of Gal-3 on EAM progression might be important in the consideration of therapeutic options for the treatment of EAM.

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Acknowledgements

We thank our colleagues Prof. Marija Milovanovic (University of Kragujevac, Serbia, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research), Prof. Zoran Milosavljevic (University of Kragujevac, Serbia, Faculty of Medical Sciences, Department of Histology and embryology), Ilija Jeftic (University of Kragujevac, Serbia, Faculty of Medical Sciences, Department of Pathophysiology), Petar Milosavljevic (Institute for medical research, Military Medical Academy, Belgrade, Serbia), and Vesna Matovic for collegial help. We also thank Miljan Nedeljkovic for excellent technical assistance.

Funding

This work was financially supported by grants from the Serbian Ministry of Science and Technological Development (ON175103 and ON17506), Serbia and Faculty of Medicine, University of Kragujevac, Serbia (Grant No. MP 01/14), and Swiss Science Foundation, No. SCOPES, IZ73ZO_152407/1.

The research was performed at Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia.

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Correspondence to Miodrag L. Lukic.

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All animal experiments were approved by the Ethical Committee of the Faculty of Medical Sciences, University of Kragujevac, Serbia (01-2630). The animal experiments were performed conform the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes.

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Kovacevic, M.M., Pejnovic, N., Mitrovic, S. et al. Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice. Immunol Res 66, 491–502 (2018). https://doi.org/10.1007/s12026-018-9013-8

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