High-Affinity IgE Receptors on Dendritic Cells Exacerbate Th2-Dependent Inflammation

The IgE-mediated and Th2-dependent late-phase reaction remains a mechanistically enigmatic and daunting element of human allergic inflammation. In this study, we uncover the Fc epsilon RI on dendritic cells (DCs) as a key in vivo component of this form of allergy. Because rodent, unlike human, DCs lack Fc epsilon RI, this mechanism could be revealed only by using a new transgenic mouse model with human-like Fc epsilon RI expression on DCs. In the presence of IgE and allergen, Fc epsilon RI(+) DCs instructed naive T cells to differentiate into Th2 cells in vitro and boosted allergen-specific Th2 responses and Th2-dependent eosinophilia at the site of allergen exposure in vivo. Thus, Fc epsilon RI on DCs drives the cascade of pathogenic reactions linking the initial allergen capture by IgE with subsequent Th2-dominated T cell responses and the development of late-phase allergic tissue inflammation. The Journal of Immunology, 2011, 187: 164-171.