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).; 2:Departamento de Biología Celular, Facultad de Biología y Medicina, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.

Galectin-1 is part of a family of carbohydrate-binding proteins, the so-called lectins, with high affinity for β-galactosides. Galectin-1 is widely expressed in many tissues and has immunomodulatory activity over different immune cell subsets that has been associated to induction of apoptosis in the target cells. Although, the immunosuppressive function of recombinant galectin-1 has been reported in many studies, the role of endogenous galectin-1 remains to be fully defined. In this study, galectin-1 deficient mice (Lgals1-/- mice) were used to investigate the in vivo function of galectin-1 in experimental colitis. Lgals1-/- mice showed enhanced susceptibility to experimental colitis with respect to WT mice as shown by the increased body weight losses and higher DAI compared to colitic WT mice. An increased plasticity of Th17 cells towards Th1 profile in DSS-induced colitic Lgals1-/- mice were determined. Strikingly, the exacerbated intestinal inflammatory responses in colitic Lgals1-/- mice was accompanied with increased frequencies of regulatory T cells in cLP. In addition, our results show that in the absence of endogenous galectin-1 an enhanced conversion of Foxp3⁺CD4⁺ Treg cells into pathogenic T-Bet-expressing Foxp3⁺CD4⁺ T cells was determined. Adoptive transfer of wild-type Foxp3⁺CD4⁺ regulatory T cells into Lgals1-/- mice during DSS-induced colitis reduces the severity of the disease, achieving a similar intestinal inflammation as to colitic WT mice. Altogether, our results highlight the relevance of the expression of endogenous galectin-1 to prevent the development of aberrant pathogenic Treg cells during the course of an intestinal inflammatory response.