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Galectin-3 suppresses mucosal inflammation and reduces disease severity in experimental colitis

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Abstract

Galectin-3, a member of the β-galactoside-binding lectin family, expresses in many different immune cells and modulates broad biological functions including cell adhesion, cell activation, cell growth, apoptosis, and inflammation. However, the role of galectin-3 in mucosal immunity or inflammatory bowel diseases is still not clear. We demonstrate here that galectin-3 knockout mice have more severe disease activity in the dextran sulfate sodium (DSS)-induced colitis model, indicating that galectin-3 may protect from inflammation in DSS-induced colitis. Furthermore, treating with galectin-3 reduced body weight loss, shortened colonic length, and ameliorated mucosal inflammation in mice having DSS-induced colitis. However, the protective effects of galectin-3 were eliminated by the administration of anti-CD25 mAb. In addition, primary T cells treated with galectin-3 ex vivo induced the expression of FOXP3, ICOS, and PD-1 with a Treg cell phenotype having a suppression function. Moreover, adoptive transfer of galectin-3-treated T cells reduced bowel inflammation and colitis in the T cell transfer colitis model. In conclusion, our results indicate that galectin-3 inhibited colonic mucosa inflammation and reduced disease severity by inducing regulatory T cells, suggesting that it is a potential therapeutic approach in inflammatory bowel disease.

Key messages

  • Galectin-3 offers protection from inflammation in experimental colitis.

  • Galectin-3 knockout mice have more severe disease activity in DSS-induced colitis.

  • Adoptive transfer of galectin-3-treated T cells reduced bowel inflammation.

  • Galectin-3 inhibited colonic mucosa inflammation by inducing regulatory T cells.

  • Galectin-3 is a potential therapeutic approach in inflammatory bowel disease.

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Acknowledgements

We thank Dr. Fu-Tong Liu (Academia Sinica, Taiwan) for kindly providing the galectin-3 knockout mice. We also thank the Department of Medical Research and core laboratory of National Taiwan University Hospital for facility support. This work was supported by grants from the National Science Council, Taiwan (NSC 98-2320-B-002-049-MY3, 100-2320-B-038-026, and 101-2321-B-002-008).

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    Authors and Affiliations

    1. Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan

      Hwei-Fang Tsai

    2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

      Hwei-Fang Tsai

    3. Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

      Chien-Sheng Wu

    4. Graduate Institute of Immunology, College of Medicine, National Taiwan University, 1 Jen-Ai Rd., Sec. 1, Taipei, 100, Taiwan

      Yi-Lin Chen, Hsiu-Jung Liao & Ping-Ning Hsu

    5. Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan

      I-Tsu Chyuan

    6. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

      Ping-Ning Hsu

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    Hwei-Fang Tsai and Chien-Sheng Wu contributed equally to this work.

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    Tsai, HF., Wu, CS., Chen, YL. et al. Galectin-3 suppresses mucosal inflammation and reduces disease severity in experimental colitis. J Mol Med 94, 545–556 (2016). https://doi.org/10.1007/s00109-015-1368-x

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