Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice.
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.
Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Campus Virchow Klinikum, Charité-Universitätsmedizin, Berlin, Germany.
Daniela
D
Paclik
Uta
U
Berndt
Claudia
C
Guzy
Anja
A
Dankof
Silvio
S
Danese
Pamela
P
Holzloehner
Stefan
S
Rosewicz
Bertram
B
Wiedenmann
Bianca M
BM
Wittig
Axel U
AU
Dignass
Andreas
A
Sturm
D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D005260:Female; D037501:Galectin 2 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D015870:Gene Expression; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D037501:Galectin 2; D016264:Dextran Sulfate