Although the alleviated colitis response could be ascribed in part to the epithelial restorative responses after injury, the dampened inflammatory response (Fig 5B, C, and E) and infiltration of the anti-inflammatory M2 macrophages (83) after DSS (Fig 5D) implicate epithelial-specific Smad4 loss in immunomodulation and suppression of the pathological inflammatory response. The gene discussed is SMAD4; the disease is colitis.