Allergic asthma is a chronic disease characterized by airway obstruction in response to allergen exposure. It results from an inappropriate T helper type 2 response to environmental airborne antigens and affects 300 million individuals1. Its prevalence has increased markedly in recent decades, most probably as a result of changes in environmental factors2. Exposure to environmental antigens during infancy is crucial to the development of asthma3. Epidemiological studies on the relationship between breastfeeding and allergic diseases have reached conflicting results4,5,6,7,8. Here, we have investigated whether the exposure of lactating mice to an airborne allergen affects asthma development in progeny. We found that airborne antigens were efficiently transferred from the mother to the neonate through milk and that tolerance induction did not require the transfer of immunoglobulins. Breastfeeding-induced tolerance relied on the presence of transforming growth factor (TGF)-β during lactation, was mediated by regulatory CD4+ T lymphocytes and depended on TGF-β signaling in T cells. In conclusion, breast milk–mediated transfer of an antigen to the neonate resulted in oral tolerance induction leading to antigen-specific protection from allergic airway disease. This study may pave the way for the design of new strategies to prevent the development of allergic diseases.
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We thank F. Powrie (University of Oxford) for D0.11.10 TCR transgenic mice and P.J. Lucas (US National Institutes of Health) for TGF-β DNRII mice. We thank F. Aguila for his help with figures and N. Guy and the animal facility staff for their excellent animal care. This work was supported by a grant from the Fondation Pour la Recherche Médicale (to V.J.) and by a grant from the European Union (DC-THERA) (to N.G.). V.V. was sponsored by fellowships from the Fondation Pour la Recherche Médicale, the US Juvenile Diabetes Research Foundation and the Belgian Fond National de la Recherche Scientifique.
Supplementary Figs. 1–6, Supplementary Table 1 and Supplementary Methods (PDF 213 kb)
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