Mechanistically, we show that IL-17R–ACT1 and IL-22R–STAT3 signaling pathways converge to the key negative regulator C/EBPβ to inhibit chemokine expression in colon epithelial cells, which prevents the pathologic breakdown of epithelial barrier in inflammatory colitis and colon cancer development. The gene discussed is IL17RA; the disease is malignant colon neoplasm.