engleski

Immunomodulatory properties of dipeptidyl peptidase IV (DPP IV/CD26) in an experimental model of ulcerative colitis

Disturbances in the balance between tolerance and an active immune response to antigens are fundamental to the pathogenesis of inflammatory bowel disease (IBD). Therefore, immune cells including dendritic cells (DC) and macrophages, as well as T cells play a crucial role in the control of intestinal inflammation and immune tolerance at both systemic and local level. A role for dipeptidyl peptidase IV (DPP IV/CD26) in the pathogenesis of IBD has been proposed owing to its involvement in immune regulations via its expression on immune cells and ability to cleave biologically active molecules. The aim of the study was to investigate the influence of DPP IV/CD26 deficiency on infiltration of specific immune cells in colonic mucosa, in a model of dextran sulfate sodium (DSS)-induced ulcerative colitis in wild-type (WT) and CD26-deficient mice. Colitis development and severity was assessed by clinical and histological parameters while distribution and expression of specific cell markers in colonic mucosa by immunohistochemical staining. In the acute phase of colitis, loss of body mass and disease activity in WT mice was more severe than in CD26-deficient mice, in spite of similar histopathological changes at the local level. Although acute inflammation induced a significant increase in the number of macrophages and DC in both mouse strains, in CD26-deficient mice the increase of macrophages was twice than in WT animals (18.0 ± 4.5 versus 41.3 ± 5.8), whereas the increase in DC was more pronounced in WT mice. Moreover, in the acute phase of inflammation an increased activation of NF-κB p65 subunit in the colonic mucosa of CD26-deficient animals was determined. Observed modulatory effect of CD26 deficiency on immune cells and activation of NF-κB p65 subunit at the site of inflammation expands current understanding and provides important insights into the role of DPP IV/CD26 in the acute phase of DSS colitis.

Dipeptidyl-peptidase IV (DPP IV/CD26); inflammatory bowel disease; ulcerative colitis

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