Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice

Abstract

Epicutaneous immunotherapy onto intact skin has proved to be an efficient and safe alternative treatment of allergy in an animal model with various allergens and in children for cow’s milk allergy. The aim of this study was to analyze the different steps of the immunological handling of the allergen when deposited on intact skin using an epicutaneous delivery system and its immune consequences in sensitized BALB/c mice. As expected, when applied on intact skin, OVA exhibits neither a passive passage through the skin nor any detectable systemic delivery. The current study demonstrates that, after a prolonged application on intact skin, OVA is taken up by dendritic cells in the superficial layers of the stratum corneum and transported, after internalization, to the draining lymph nodes, with variations according to the previous level of sensitization of the mice. When OVA is applied with the epicutaneous delivery system repeatedly, specific local and systemic responses are down-modulated in association with the induction of regulatory T cells. Besides providing new insights into skin function in the presence of allergens, this study indicates that the skin might have a tolerogenic role, at least when kept intact.

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

“…In addition, in mouse models of sublingual immunotherapy, the allergen is captured within the oral mucosa by LC-like DCs producing IL-10 and TGF-β, and upregulating IDO, suggesting that such cells contribute to the efficacy of these promising treatments (53). More recently, epicutaneous delivery of a protein Ag through intact skin via an occlusive chamber was found to favor uptake by epidermal DCs reaching the superficial layers of the stratum corneum and to reduce allergen-specific responses in sensitized mice (54). In view of our data and the aforementioned observations, it may thus be anticipated that strategies that exploit, or even increase, the tolerogenic functions of epithelial LCs could be of invaluable interest in developing innovative treatments for human allergic diseases.…”

Epicutaneous Sensitization Results in IgE-Dependent Intestinal Mast Cell Expansion and Food Anaphylaxis

“…In contrast to EC sensitization of tape stripped skin, antigen uptake via intact skin downregulates the allergen-specific response in previously sensitized mice. 23 The fact that EC sensitized mice anaphylaxed to a single oral challenge in an IgE-dependent manner makes our model highly relevant to human IgE-mediated food anaphylaxis. In previous reports of IgE mediated anaphylaxis in WT mice, 24, 25 the mice were i.p.…”

Immunomodulatory Effect of Active Treatment Options in Food Allergy

“…Little is known about the immune mechanisms of EPIT in humans, but the mechanism of action as defined in murine studies is believed to be through activation of local Langerhans cells that migrate to regional lymph nodes and downregulate the immune response [87]. In a study of peanut-sensitized mice, the use of EPIT significantly decreased peanut-specific IgE and increased peanut-specific IgG2 compared with sham-treated mice [88,89].…”