Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease (IBD), complete mucosal healing occurs in less than 50% of patients. The Fc region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We examined the interaction between the anti-TNF Fc region and Fcγ receptors (FcγR), and whether the absence of the Fc core fucose (which increases binding to FcγRIIIa) increases the efficacy of anti-TNF in mice with colitis.