Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma.
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 individuals. Its prevalence has increased markedly in recent decades, most probably as a result of changes in environmental factors. Exposure to environmental antigens during infancy is crucial to the development of asthma. Epidemiological studies on the relationship between breastfeeding and allergic diseases have reached conflicting results. 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)-beta during lactation, was mediated by regulatory CD4+ T lymphocytes and depended on TGF-beta 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.
Verhasselt
Valérie
V
Institut National de la Santé et de la Recherche Médicale, U924, Université de Nice-Sophia Antipolis, Valbonne, France. verhasselt@unice.fr
Milcent
Valérie
V
Cazareth
Julie
J
Kanda
Akira
A
Fleury
Sébastien
S
Dombrowicz
David
D
Glaichenhaus
Nicolas
N
Julia
Valérie
V
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D007108:Immune Tolerance / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D007774:Lactation; D018811:Maternal Exposure; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008892:Milk / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000941:Antigens; D007136:Immunoglobulins; D010047:Ovalbumin