IL-10- and retinoic acid-induced regulatory dendritic cells are therapeutically equivalent in mouse models of asthma and food allergy

IL-10-induced DC (DC10) secrete IL-10, thereby promoting aeroallergen tolerance by activation of CD25+Foxp3+ Treg, while retinoic acid-induced DC (DC-RA) foster food allergen tolerance via IL-27-dependent induction of Foxp3− Treg. In some respects, these outcomes reflect those seen with aero- or food allergen-presenting lung and intestinal DC, respectively. Herein we asked whether these DCreg would also be functional in their reciprocal settings. DC-RA expressed lower levels of CCR5, CCR9, and CD103 than DC10, but higher levels of CD40, CD86, MHC II, TGF-β, IL-27 and Aldh1A2. DC-RA were also more effective in suppressing OVA-specific T cell proliferation in vitro (p ≤ 0.05). Co-culture of DC10 or DC-RA with OVA-specific T cells activated a regulatory phenotype therein, with the DC-10-induced Treg being modestly more suppressive in vitro than the DC-RA-induced Treg. We previously reported on lung trafficking of DC10, but DC-RA also traffic through the lungs and mediastinal lymph nodes before accumulating in the mesenteric lymph nodes. Both DCreg populations equally reduced airway hyperresponsiveness, Th2 responses (Th2 cytokines, eosinophilia) to airway allergen challenge, and plasma IgE/IgG1 levels in an OVA-asthma model. Similarly, they were equally effective in our OVA-food allergy model, where they reduced clinical scores (p ≤ 0.001), mast cell activation (p ≤ 0.05) and Th2 cytokine responses to allergen challenge, as well as OVA-specific IgE/IgG1 levels (p ≤ 0.01). Taken together, this data indicates that while DC10 and DC-RA employ distinct operative mechanisms, they were both able to induce tolerance in lung- and gut-associated allergic disease.