Abstract

The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT) with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins) upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response.

Highlights

  • The prevalence of food allergies has increased over the last decade and constitutes a highly morbid disorder. [1]

  • Animals were sensitized with milk proteins and hypersensitivity reactions observed immediately after the oral challenges with cow’s milk proteins (CMP) were scored (Fig 1B)

  • CMPprev mice were protected from allergy and CMPdes mice showed a high score

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Summary

Introduction

The prevalence of food allergies has increased over the last decade and constitutes a highly morbid disorder. [1]. The restriction diet represents the current treatment for milk-allergic children, but it may be difficult to comply for multiple reasons: misunderstanding or incomplete information in food labeling, nutritional inadequacy of dairy substitutes, growth retardation, eating disorders and psychosocial problems [2]. For this reason, efforts have been made to develop alternative therapies that complement the avoidance strategy and restore an adequate immune management of food antigens.

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