Despite numerous therapeutic advancements, inflammatory bowel disease (IBD) remains a major health burden due to the inefficiency of conventional therapies. We recently demonstrated the role of death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily and receptor for the cytokine TL1A, in regulating the balance between effector [T helper type 1 (TH)1,TH2,TH17] and regulatory T cells during murine Crohn’s disease (CD)-like ileitis. New evidence suggests a potential role of IL-9-secreting TH9 cells in the pathogenesis of IBD.