Enhanced Susceptibility of Galectin-1 Deficient Mice to Experimental Colitis.

Raquel Fernandez-Perez,Omaira Alberquilla,Rebeca Sánchez-Domínguez,Yasmina Juarranz,Irene Gutiérrez-Cañas,Marina I Garin,Mercedes Lopez-Santalla,Juan A Bueren

doi:10.3389/fimmu.2021.687443

Abstract

Galectin-1 is a β-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 β-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 (Lgals1−/− 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 Lgals1−/− mice involved an altered Th17/Th1 profile of effector CD4+ T cells. Furthermore, increased frequencies of Foxp3+CD4+ regulatory T cells in colon lamina propria in Lgals1−/− mice were found. Strikingly, the exacerbated intestinal inflammatory response observed in Lgals1− / − mice was alleviated by adoptive transfer of wild type Foxp3+CD4+ 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.

Highlights

Galectins are among the best-characterized glycan-binding proteins that play key roles in multiple immune cell processes [1]
Rabinovich and collaborators have extensively demonstrated that galectin-1 can control the proliferation of Th17, Th1, and cytotoxic CD8+ effector T cell responses but not on naïve, Th2 or regulatory T cells, thanks to an activation-specific repertoire of glycans expressed in their cell membrane glycoproteins that are essential for galectin-1 specific binding [12, 13]
To investigate whether endogenous galectin-1 plays a role in experimental colitis, wild type (WT) and Lgals1−/− mice were

Summary

Introduction

Galectins are among the best-characterized glycan-binding proteins that play key roles in multiple immune cell processes [1]. They formed a family of 15 mammalian galactoside-binding proteins that exhibit a consensus amino acid sequence in their carbohydrate recognition domains (CRDs) [2]. Rabinovich and collaborators have extensively demonstrated that galectin-1 can control the proliferation of Th17, Th1, and cytotoxic CD8+ effector T cell responses but not on naïve, Th2 or regulatory T cells, thanks to an activation-specific repertoire of glycans expressed in their cell membrane glycoproteins that are essential for galectin-1 specific binding [12, 13]

Methods

Results

Conclusion