Langerhans cells mediate the skin‐induced tolerance to ovalbumin via Langerin in a murine model

Abstract Background Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen‐specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin‐induced tolerance is not fully understood. Methods Langerin‐DTA mice that were deficient in LCs were utilized to produce the model of skin‐induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme‐linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin‐DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin‐induced tolerance. Results Application with OVA onto the intact, but not tape‐stripped, skin attenuated the production of OVA‐specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin‐DTA mice. In contrast to the tape‐stripped skin, the intact skin induced the production of IL‐10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin‐DTR mice demonstrated similar humoral and cellular immune responses in the model of skin‐induced tolerance compared to wide‐type mice. Conclusion Our data suggested that LCs were critical in the intact skin‐induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases.