Tu1753 - type 1 Interferon Signaling in Intestinal Epithelial Cells During Active Inflammatory Bowel Disease

epithelium.Immunohistochemistry was used to assess the cellularity and architecture of colons from Zfp36 D IEC mice.Control Zfp36 fl/fl mice and Zfp36 D IEC mice were treated with 2% DSS for 5 days followed by 5 days of recovery.Weight loss and disease activity indices were measured daily, and colon length was measured on day 10.Western blot and immunohistochemical analysis was conducted on colon tissue from day 10.Results: The colons of juvenile Zfp36 D IEC mice exhibited increased crypt depth and a mild expansion of the proliferative zone.This coincided with an increased number of goblet cells per crypt.Resident neutrophil and macrophage populations in the colons of Zfp36 D IEC mice were normal as was expression of known TTP target genes, except a slight elevation of TNF a. Strikingly, when Zfp36 D IEC mice were challenged with DSS, they displayed less weight loss, significantly lower disease activity indices, and markedly reduced colon shortening in comparison to control Zfp36 fl/fl mice.After the recovery period, the colonic mucosal architecture of Zfp36 DIEC mice was restored to near baseline, whereas Zfp36 fl/fl mice had substantial residual immune infiltration, fewer crypt structures, and reduced numbers of goblet cells.Conclusions: We demonstrate that TTP expression in the intestinal epithelium promotes DSS-induced colitis.These results are unanticipated given the established anti-inflammatory function of TTP in immune cells.We show that epithelial TTP impairs regeneration of the mucosal barrier, possibly by repressing cellular proliferation.These findings bring to question therapeutic strategies aimed at restoring TTP function and emphasize the pleiotropic function of a critical RNA binding protein.