Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy

While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4(+)Foxp3(+) regulatory T (T(reg)) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4(+)Foxp3(+) T(reg) cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b(+) cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4(+)Foxp3(+) T(reg) cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b(+) conventional dendritic cells.