• Immunological and Potentially Therapeutic Aspects of Galectins in Graft-versus-Host Disease
  • Yeganeh Lalehzari,1,*
    1. Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.


  • Introduction: Graft-versus-host disease (GVHD) remains a major challenge in allogeneic hematopoietic stem cell transplantation, often limiting its success despite advances in transplantation protocols. Galectins—a family of carbohydrate-binding proteins—have gained attention for their diverse immunomodulatory roles, influencing both inflammatory and regulatory pathways. This systematic review aims to synthesize current evidence on the immunological functions of galectins in GVHD and to explore their potential as therapeutic targets.
  • Methods: In this article, data were collected by using keywords and using databases such as Google Scholar, PubMed, Scopus, ProQuest and Web of Science for articles published up to July 2025. Studies were included if they investigated the role of any galectin in the context of GVHD, including experimental models, clinical data, and therapeutic approaches. Data extraction focused on galectin expression patterns, immune cell interactions, cytokine modulation, and clinical outcomes.
  • Results: Twenty-seven studies met the inclusion criteria, highlighting the contrasting roles of different galectin isoforms in GVHD. Galectin-1 was consistently associated with immune tolerance, promoting apoptosis of effector T cells and enhancing regulatory T cell function. Galectin-3, in contrast, appeared to exacerbate GVHD through pro-inflammatory signaling and tissue damage. Galectin-9 emerged as a promising immunoregulatory molecule, particularly through its interaction with TIM-3, attenuating T cell responses and supporting immune balance. Galectin-9 ameliorates aGVHD after haplo‐HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Several preclinical studies reported that galectin modulation could alleviate GVHD symptoms without compromising the beneficial graft-versus-leukemia effect.
  • Conclusion: Galectins play multifaceted roles in shaping the immune landscape of GVHD, acting as both regulators and potential drivers of disease severity depending on their isoform and cellular context. Targeting specific galectin pathways offers a novel and potentially safer approach to GVHD management. However, further clinical trials are needed to validate these findings and optimize therapeutic strategies.
  • Keywords: Graft versus Host Disease, Galectin, Galectin-1, Galectin-3, Galectin-9.