Determining the Role of the Transcription Factor Cdx2 in the Development of Colitis

Abstract

Cdx2 is an intestine-specific homeodomain-containing transcription factor that is essential for intestinal patterning and homeostasis. Recent findings indicate that Cdx2 regulates intestinal inflammation and suggest an involvement in Inflammatory Bowel Disease (IBD). To investigate this role, the Dextran Sulphate Sodium (DSS)-induced colitis model was used to examine the impact of Cdx2 status on intestinal barrier function, immune responses, and gene regulation, to determine whether Cdx2 suppresses inflammatory pathways that exacerbate colitis. Cdx2- dependent alterations in gene expression were identified using RNA-seq and candidate Cdx2 target genes were identified by cross-referencing to previously generated ChIP-seq data. The findings demonstrate that Cdx2 loss and DSS treatment often independently alter intestinal permeability, barrier function, immune infiltration, and gene expression, suggesting distinct mechanisms of action. These results provide new insight into Cdx2 function in intestinal homeostasis, inflammation and IBD pathogenesis.