Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4341
Peer-review started: June 21, 2018
First decision: August 1, 2018
Revised: August 6, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 14, 2018
Processing time: 113 Days and 12.8 Hours
To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis.
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.
Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in pro-inflammatory 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.
Core tip: Our study contributes to a better understanding of the dextran sulfate sodium (DSS) acute colitis model in order to provide a stronger basis for novel therapies. Colonic proteomic temporal analysis reveals an increase in cytokines with a strong influx of immune cells. The highest cytokine levels were observed when animals were no longer drinking DSS, suggesting a rebound response. Secondary lymphoid organs contribute by sending different immune cells to the colon during the acute phase, such as CD4+, CD8+ and CD25+ T cells. Our results demonstrate involvement of the adaptive and innate immune responses during the acute phase of DSS-induced colitis.