DAB2IP modulates intestinal inflammation by enhancing ILC3 function in the gut

Group 3 innate lymphoid cells (ILC3s) protect the intestinal barrier by producing IL-22 and IL-17A, yet the molecular mechanisms that sustain their cytokine output during inflammation remain poorly defined. Here, we identify the cytosolic scaffold DAB2IP as a critical ILC3-intrinsic regulator of effector function. In human IBD, DAB2IP expression is reduced in inflamed tissues, correlating with impaired epithelial repair and decreased IL-22. In mice, DAB2IP expression in ILC3s declines during intestinal inflammation, and silencing DAB2IP markedly diminishes IL-22 and IL-17A production. Adoptive transfer of Dap2ip-deficient ILC3s exacerbates DSS-induced colitis and increases susceptibility to Citrobacter rodentium. Mechanistically, DAB2IP promotes NF-κB activation, sustaining transcription of Il22 and Il17a. These results reveal a context-dependent role for DAB2IP as a positive regulator of NF-κB in ILC3s, highlighting its previously unknown function in mucosal immunity and epithelial repair, and suggesting that restoring DAB2IP signaling could enhance barrier protection during intestinal inflammation.