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.

Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis

“…A recent study showed that LCs played an immunosuppressive role when OVA was applied on the intact skin, in company with the induction of IL-10 in LCs in skin-draining LNs. 72 However, this does not seem to be our case, because Langerin 1 migDCs in EDLN did not exhibit any transcriptional change of regulatory T cell-inducing signals including IL-10 and TGF-b, or ALDH1A2. More likely, the anti-T FH /T H 2 effect of LCs is related to their immune suppression function in situ in the skin, in keeping with LC ontogeny not only as DCs but also as nonmigratory macrophages.…”

Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy

“…Upon antigen uptake, these DCs can migrate to local lymph nodes where they exert classical DC functions and drive adaptive responses to food antigens (18). Dermal CD11b+ DCs as well as Langerhans cells play a central role in the induction of tolerance to allergens in the skin (19)(20)(21).…”

Epicutaneous vaccination with protease inhibitor-treated papain prevents papain-induced Th2-mediated airway inflammation without inducing Th17 in mice

“…Recent studies suggested involvement of Langerhans cells and regulatory T cells in prophylactic and therapeutic models with e.c. OVA administration [29,30]. Interestingly, e.c.…”