Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites.

ABSTRACT: Antigen-mediated cross-linking of Immunoglobulin E (IgE) bound to mast cells/basophils via Fc?RI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express Fc?RI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/Fc?RI signals for DC function remain poorly understood. We show that humanized mice that express Fc?RI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/Fc?RI cross-linking fails to induce maturation or production of inflammatory mediators in human DCs and Fc?RI-humanized DCs. Furthermore, conferring expression of Fc?RI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/Fc?RI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/Fc?RI cross-linking on papain or lipopolysaccharide-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in Fc?RI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation.

SUBMITTER: Platzer B 

PROVIDER: S-EPMC4363306 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature