Enhanced susceptibility of galectin-1 deficient mice to experimental colitis

Abstract

Galectin-1 is a<jats:italic>β</jats:italic>-galactoside-binding lectin, ubiquitously expressed in stromal, epithelial, and different subsets of immune cells. Galectin-1 is the prototype member of the galectin family which shares specificity with<jats:italic>β</jats:italic>-galactoside containing proteins and lipids. Immunomodulatory functions have been ascribed to endogenous galectin-1 due to its induction of T cell apoptosis, inhibitory effects of neutrophils and T cell trafficking. Several studies have demonstrated that administration of recombinant galectin-1 suppressed experimental colitis by modulating adaptive immune responses altering the fate and phenotype of T cells. However, the role of endogenous galectin-1 in intestinal inflammation is poorly defined. In the present study, the well-characterized acute dextran sulfate sodium (DSS)-induced model of ulcerative colitis was used to study the function of endogenous galectin-1 during the development of intestinal inflammation. We found that galectin-1 deficient mice (<jats:italic>Lgals1<jats:sup>−/−</jats:sup></jats:italic>mice) displayed a more severe intestinal inflammation, characterized by significantly elevated clinical scores, than their wild type counterparts. The mechanisms underlying the enhanced inflammatory response in colitic<jats:italic>Lgals1<jats:sup>−/−</jats:sup></jats:italic>mice involved an altered Th17/Th1 profile of effector CD4<jats:sup>+</jats:sup>T cells. Furthermore, increased frequencies of Foxp3<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>regulatory T cells in colon lamina propria in<jats:italic>Lgals1<jats:sup>−/−</jats:sup></jats:italic>mice were found. Strikingly, the exacerbated intestinal inflammatory response observed in<jats:italic>Lgals1<jats:sup>−</jats:sup></jats:italic><jats:sup>/</jats:sup><jats:italic><jats:sup>−</jats:sup></jats:italic>mice was alleviated by adoptive transfer of wild type Foxp3<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>regulatory T cells at induction of colitis. Altogether, these data highlight the importance of endogenous galectin-1 as a novel determinant in regulating T cell reactivity during the development of intestinal inflammation.