It is well-established that microbiota and immune cells signal to colon epithelial cells to increase production of chemokines and pro-inflammatory cytokines that can accelerate inflammation, but we have found that TGFβ/SMAD4 signaling in colon epithelium can suppress inflammation by negatively regulating pro-inflammatory gene expression. TGFβ and related cytokines activate type I and type II receptors that then phosphorylate R-SMADs. When phosphorylated, R-SMADs must then form a complex with SMAD4 to act as transcriptional activators or repressors.