Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice

Abstract

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.

Galectin-2 Suppresses Contact Allergy by Inducing Apoptosis in Activated CD8+ T Cells

“…Galectins have recently emerged as important players during immune responses, and it has been demonstrated that galectin-2 regulates cell-mediated inflammatory bowel disease and colitis in mice (20,31). Since we have shown that galectin-2 is expressed in murine skin and, most importantly, is significantly up-regulated upon cutaneous inflammation ( Fig.…”

“…In that model, Ag-specific MHC class II-restricted T cells were transferred into naive recipients, which were subsequently challenged with the cognate Ag. In colitis, galectin-2 was able to inhibit the effector function of CD4 ϩ T cells (20,31). In contrast to experimental colitis, galectin-2 suppressed, in the model of contact allergy, activated CD8 ϩ T cells rather than CD4 ϩ T cells.…”

“…Collectively, the results from both models show that galectin-2 can control inflammation at both interfaces, that is, the skin and the intestine. Perhaps intestinal galectin-2 expression plays an additional role in tissue homeostasis since it was demonstrated that galectin-2 is able to regulate the function of lamina propria lymphocytes (31).…”

“…Cell adhesion studies using galectin-2-treated human T cells from peripheral blood or intestinal lamina propria and collagen type I or fibronectin as matrix compounds showed differential effects. Galectin-2 reduced the binding of both human T cell subpopulations to collagen matrix; in contrast, binding to fibronectin was significantly enhanced (20,31). It was proposed that galectin-2 might be able to bridge glycan chains of matrix compounds and cell surface glycoproteins.…”

Galectins: Key Players at the Frontiers of Innate and Adaptive Immunity

“…Gal2 is preferentially expressed on epithelial cells of the gastrointestinal tract suggesting a potential role for this lectin in the regulation of mucosal immunity (55). In this regard, administration of recombinant Gal2 ameliorates clinical manifestations of experimental colitis by impairing viability of lamina propria T cells (55).…”