Induced intra-epithelial lymphocytes (iIELs) are widely distributed within the intestinal epithelial cell (IEC) layer. However, differentiation and function of iIELs in healthy individuals and their role within the pathogenesis of inflammatory bowel diseases (IBD) await to be fully elucidated. We found that selected deficiencies within the conventional DC (cDC1) compartment result in distinct iIEL pool alterations. Hence, employing cDC1-targeted mice as iIEL deficiency model systems we seek to study the molecular mechanisms and functional consequences of the iIEL-IEC crosstalk during intestinal homeostasis and inflammation.