Different populations of CD11b⁺ dendritic cells drive Th2 responses in the small intestine and colon

T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4^f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4^f/f CD11c-cre mice have fewer CD11b⁺ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b⁺CD103⁺ DCs induce Th2 responses in the small intestine, whereas CD11b⁺CD103^- DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.