Breast milk–mediated transfer of an antigen induces tolerance and protection from allergic asthma

Abstract

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.

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

“…Cite this article as Cold Spring Harb Perspect Biol 2017;9:a022236 Hughes et al 2000;Saarinen et al 2000;Ogawa et al 2004;Verhasselt et al 2008;Verhasselt 2010;Arnold et al 2011). …”

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

“…A reciprocal process, trafficking of maternal cells across the placenta, has also been documented (4,5) and can result in life-long microchimerism in the offspring (6). In addition, maternal cells and HLA proteins are ingested by the baby during nursing, possibly stimulating oral tolerance (7,8). However, the mechanisms by which NIMAs actually drive the immune system toward tolerance or rejection of allograft are still unclear.…”

“…In contrast, Kanda et al (15) described that a substantial proportion of long-term survivors after NIMA-mismatched HSCT could discontinue administration of immunosuppressive agents despite the frequent occurrence of moderate to severe chronic GVHD. Thus, the immunologic effects of developmental exposure to NIMAs are heterogeneous (8,16,17).…”

Development of the Immune System - Early Nutrition and Consequences for Later Life

“…To guarantee the uptake of TGF , TGF receptors are abundantly expressed in the neonatal intestine, even the soluble TGF 2 receptor is present in breast milk. But in addition it was found that TGF is not essential for tolerance induction when milk born-IgG antigen immune complexes are present (Verhasselt, Milcent et al 2008). Moreover it is known that high levels of TGF together with RA skew the immune system towards a regulatory suppressive function, a low dose of TGF combined with IL6 or IL21 or IL23 will result in inflammatory Th17 activation instead of Treg upregulation (Konkel and Chen 2011).…”