Dendritic cell–specific deletion of PKCδ in offspring of allergic mothers prevents the predisposition for development of allergic lung inflammation in offspring.

In humans and in mice, maternal allergy predisposes offspring to development of allergy. In murine models, increased levels of maternal β-glucosylceramides are both necessary and sufficient for the development of allergic predisposition in offspring. Furthermore, increased numbers of CD11b+ dendritic cell subsets in the offspring of allergic mothers are associated with allergic predisposition. In vitro, β-glucosylceramides increase CD11b+ dendritic cell subset numbers through increased PKCδ signaling, but it is not known if enhanced PKCδ signaling in dendritic cells is required in vivo. We demonstrate that dendritic cell–specific deletion of PKCδ prevents the β-glucosylceramide–induced increase in CD11b+ dendritic cell subset numbers both in vitro as well as in vivo in the fetal liver of offspring of mothers injected with β-glucosylceramides. Furthermore, dendritic cell–specific deletion of PKCδ in offspring prevents the maternal allergy–induced increase in CD11b+ dendritic cell subsets and decreases allergen-induced interleukin-5 and eosinophilia in lungs of offspring. However, loss of PKCδ in dendritic cells did not prevent development of allergen-specific IgE. Our study provides mechanistic insight into the function of PKCδ in the origins of allergic disease beginning in utero as well as in the development of postnatal allergic lung inflammation. [ABSTRACT FROM AUTHOR]