Abstract
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 (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg 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+ Treg 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.
Highlights
While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear
To clarify whether SLIT is effective for the treatment of other TH2-mediated allergic disorders, we investigated the protective effect of SLIT on the development of food allergy and systemic anaphylaxis
Because the transfer of fed antigens from CX3CR1+ macrophages to CD103+ conventional DCs (cDCs) has been reported in the intestinal mucosa for the establishment of oral tolerance[32], we examined the influence of the depletion of oral macrophages on the activation of antigen-specific CD4+ T cells in migratory cDCs in draining submandibular lymph nodes (ManLNs) following sublingual antigenic application
Summary
While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Several subsets of macrophages and cDCs in sublingual mucosal tissues have been considered to capture antigens to generate TH1 cells and/or CD4+Foxp3+ Treg cells following sublingual antigenic application[23,24,25,26,27], how migratory cDCs in draining submandibular lymph nodes (ManLNs) control allergic immune responses currently remains unclear even in the mouse model of SLIT.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
