Jagged1‐expressing adenovirus‐infected dendritic cells induce expansion of Foxp3 + regulatory T cells and alleviate T helper type 2‐mediated allergic asthma in mice

Summary Dendritic cells ( DC s) are professional antigen‐presenting cells that play a key role in directing T‐cell responses. Regulatory T (Treg) cells possess an immunosuppressive ability to inhibit effector T‐cell responses, and Notch ligand Jagged1 (Jag1) is implicated in Treg cell differentiation. In this study, we evaluated whether bone marrow‐derived DC s genetically engineered to express Jag1 (Jag1‐ DC s) would affect the maturation and function of DC s in vitro and further investigated the immunoregulatory ability of Jag1‐ DC s to manipulate T helper type 2 (Th2) ‐mediated allergic asthma in mice. We produced Jag1‐ DC s by adenoviral transduction. Overexpression of Jag1 by ovalbumin ( OVA ) ‐stimulated Jag1‐ DC s exhibited increased expression of programmed cell death ligand 1 ( PD ‐L1) and OX 40L molecules. Subsequently, co‐culture of these OVA ‐pulsed Jag1‐ DC s with allogeneic or syngeneic CD 4 + T cells promoted the generation of Foxp3 + Treg cells, and blocking PD ‐L1 using specific antibodies partially reduced Treg cell expansion. Furthermore, adoptive transfer of OVA ‐pulsed Jag1‐ DC s to mice with OVA ‐induced asthma reduced allergen‐specific immunoglobulin E production, airway hyperresponsiveness, airway inflammation, and secretion of Th2‐type cytokines (interleukin‐4, interleukin‐5, and interleukin‐13). Notably, an increased number of Foxp3 + Treg cells associated with enhanced levels of transforming growth factor‐ β production was observed in Jag1‐ DC ‐treated mice. These data indicate that transgenic expression of Jag1 by DC s promotes induction of Foxp3 + Treg cells, which ameliorated Th2‐mediated allergic asthma in mice. Our study supports an attractive strategy to artificially generate immunoregulatory DC s and provides a novel approach for manipulating Th2 cell‐driven deleterious immune diseases.