CX3CR1 is required for airway inflammation by promoting T helper cell survival and maintenance in inflamed lung.

Allergic asthma is a T helper type 2 (T(H)2)-dominated disease of the lung. In people with asthma, a fraction of CD4(+) T cells express the CX3CL1 receptor, CX3CR1, and CX3CL1 expression is increased in airway smooth muscle, lung endothelium and epithelium upon allergen challenge. Here we found that untreated CX3CR1-deficient mice or wild-type (WT) mice treated with CX3CR1-blocking reagents show reduced lung disease upon allergen sensitization and challenge. Transfer of WT CD4(+) T cells into CX3CR1-deficient mice restored the cardinal features of asthma, and CX3CR1-blocking reagents prevented airway inflammation in CX3CR1-deficient recipients injected with WT T(H)2 cells. We found that CX3CR1 signaling promoted T(H)2 survival in the inflamed lungs, and injection of B cell leukemia/lymphoma-2 protein (BCl-2)-transduced CX3CR1-deficient T(H)2 cells into CX3CR1-deficient mice restored asthma. CX3CR1-induced survival was also observed for T(H)1 cells upon airway inflammation but not under homeostatic conditions or upon peripheral inflammation. Therefore, CX3CR1 and CX3CL1 may represent attractive therapeutic targets in asthma.

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.