We assessed the role of CCR5+/CCR6+/CD11b+/CD11c+ dendritic cells (DCs) for induction of ovalbumin (OVA)-specific antibody (Ab) responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL) showed early expansion of CCR5+/CCR6+/CD11b+/CD11c+ DCs in nasopharyngeal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs). Subsequently, this DC subset became resident in submandibular glands (SMGs) and nasal passages (NPs) in response to high levels of CCR-ligands produced in these tissues. CD11b+/CD11c+ DCs were markedly decreased in both CCR5-/- and CCR6-/- mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR) and CCR5-/- or CD11c-DTR and CCR6-/- mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA)Ab responses in saliva and nasal washes. These results suggest that CCR5+CCR6+ DCs play an important role in the induction of Ag-specific SIgA Ab responses. © 2013 Fukuyama et al.