BACKGROUND:: OBJECTIVE:: METHODS:: Oral tolerance was induced by DNFB gavage in germ-free and mice deficient in several TLRs. Tolerance was assessed by means of suppression of contact hypersensitivity and hapten-specific IFN-γ–producing effector T cells. The tolerogenic function of intestinal DCs was tested by adoptive transfer experiments, ex vivo hapten presentation, and forkhead box p3 regulatory T-cell conversion. RESULTS:: Oral tolerance induced by DNFB gavage was impaired in germ-free mice and TLR4-deficient mice. Bone marrow chimeras revealed that TLR4 expression on hematopoietic cells was necessary for oral tolerance induction. TLR4 appeared to be essential for the ability of intestinal dendritic cells from DNFB-fed mice to inhibit ACD on adoptive transfer. Indeed, TLR4 conditioned the in vivo mobilization to mesenteric lymph nodes of intestinal migratory CD103 DCs carrying oral DNFB, especially the CD103CD11b DC subset expressing the vitamin A–converting enzyme retinaldehyde dehydrogenase and specialized in forkhead box p3–positive regulatory T-cell conversion. CONCLUSIONS