Background:: Galectins are involved at different stages in inflammation. Galectin‐3, although mostly described as proinflammatory, can also act as an immunomodulator by inducing apoptosis in T cells. The present study aims to determine galectin‐3 expression in the normal and inflamed intestinal mucosa and to define its role in T cell activity. Materials and Methods: Galectin‐3 was detected by quantitative polymerase chain reaction with total RNA from endoscopic biopsies and by immunohistochemistry. Biopsies and peripheral blood mononuclear cells (PBMC) were stimulated in vitro and were used to assess the functional consequences of inhibition or exogenous addition of galectin‐3. Results: Galectin‐3 is expressed at comparable levels in controls and inflammatory bowel disease (IBD) patients in remission. In the normal mucosa, galectin‐3 protein was mainly observed in differentiated enterocytes, preferentially at the basolateral side. However, galectin‐3 was significantly downregulated in inflamed biopsies from IBD patients. Ex vivo stimulation of uninflamed biopsies with tumor necrosis factor led to similar galectin‐3 messenger RNA downregulation as in vivo. When peripheral blood mononuclear cells (PBMC) were analyzed, galectin‐3 was mainly produced by monocytes. Upon mitogen stimulation, we observed increased proliferation and decreased activation‐induced cell death of peripheral blood T cells in the presence of galectin‐3‐specific small interfering RNA. In contrast, exogenous addition of recombinant galectin‐3 led to reduced proliferation of mitogen‐stimulated peripheral blood T cells. Conclusions: Our results suggest that downregulation of epithelial galectin‐3 in the inflamed mucosa reflects a normal immunological consequence, whereas under noninflammatory conditions, its constitutive expression may help to prevent inappropriate immune responses against commensal bacteria or food compounds. Therefore, galectin‐3 may prove valuable for manipulating disease activity.
1 Department of Clinical Research, Division of Gastroenterology, University Hospital, University of Bern, Switzerland
2 Institute of Pathology, Division of Clinical Histopathology, University of Bern, Bern, Switzerland
*Reprints: Department of Clinical Research, Division of Gastroenterology, University of Bern, Murtenstrasse 35, C811, CH‐3010 Bern, Switzerland
Received 7 April 2006; Accepted 10 April 2006
This work was supported by a grant from the Novartis Stiftung für medizinisch‐biologische Forschung.