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Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice

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Abstract

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.

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Acknowledgments

We thank Annett Rexin for technical assistance, Christoph Loddenkemper for histological analysis, and Christian Müller for biochemical analysis.

Competing interests

None.

Funding

This work was supported by a grant from the Broad Medical Research Program of The Eli and Edythe Broad Foundation, the Bundesministerium für Forschung and Technologie (BMFT; AS), and by the Forschungsförderung of the Charité, Universitätsmedizin Berlin (AS).

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Authors and Affiliations

  1. Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Campus Virchow Klinikum, Charité-Universitätsmedizin, Berlin, Germany

    Daniela Paclik, Uta Berndt, Claudia Guzy, Stefan Rosewicz, Bertram Wiedenmann, Axel U. Dignass & Andreas Sturm

  2. Institut für Pathologie, Campus Mitte, Charité-Universitätsmedizin, Berlin, Germany

    Anja Dankof

  3. Division of Gastroenterology, Instituto Clinico Humanitas-IRCCS, Milan, Italy

    Silvio Danese

  4. Medizinische Klinik 1 (Gastroenterologie, Infektiologie und Rheumatologie), Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany

    Pamela Holzloehner & Bianca M. Wittig

  5. Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Andreas Sturm

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  1. Daniela Paclik
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Correspondence to Andreas Sturm.

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Paclik, D., Berndt, U., Guzy, C. et al. Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice. J Mol Med 86, 1395–1406 (2008). https://doi.org/10.1007/s00109-007-0290-2

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  • DOI: https://doi.org/10.1007/s00109-007-0290-2

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