Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

Abstract

AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis. METHODS Acute colitis was induced in C57BL/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon. RESULTS Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in proinflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80+, T helper CD4+ (Th), T cytotoxic CD8+ (Tcyt) and T regulatory CD25+ (Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/ or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut. These results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS.