1:Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Centre for Biomedical Network Research on Rare Diseases (CIBER-ER) and Advanced Therapy Unit, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM).

Cell therapy with regulatory T cells (Tregs) is under intense development thanks to their potential to maintain peripheral tolerance and their capacity to modulate unwanted immune responses. Galectin-1 (Gal-1) is a β-galactoside-binding protein that has broad anti-inflammatory and pro-resolving activities by targeting glycoproteins expressed by immune cells. We have previously demonstrated that Gal-1 is expressed by regulatory T cells and contributes to their immunosuppressive function in vitro. In this study, we analyzed the ability of galectin-1 deficient CD4⁺CD25⁺Foxp3 Tregs (Lgals1^-/- Tregs) to suppress gastrointestinal immune responses using a T-cell transfer model of experimental colitis to study their functionality in vivo. Lgals1^-/-Tregs showed reduced immunomodulatory capacity compared to wild type Tregs, as suggested by the increase number of Lgals1^-/- Tregs required to modulate intestinal inflammation induced by naïve CD4⁺ T cells into Rag-1^-/- mice. In addition, long-term survival of colitic mice treated with Lgals1^-/- Tregs was compromised with respect to colitic mice treated with wild type Tregs mainly due to a systemic decline in Lgals1^-/- Tregs, which paralleled to an increase in Th17 T cells frequencies in colon lamina propria and in spleen. These results indicate that galectin-1 is a key effector molecule in Tregs that is also required for long-term protection in chronic colitis. In summary, an adequate expression of galectin-1 should be analyzed in future cell therapy protocols with Tregs in inflammatory bowel disease.