SUMMARY: The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ and CD4CD8αα T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103CD11b DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis. GRAPHICAL ABSTRACT: (Figure is included in full-text article.) HIGHLIGHTS: : Classical dendritic are central regulators of adaptive immune responses. Here Agace and colleagues demonstrate multiple roles for IRF8 transcription factor-dependent classical DCs in intestinal adaptive immune homeostasis.