| First Author | Platzer B | Year | 2015 |
| Journal | Mucosal Immunol | Volume | 8 |
| Issue | 3 | Pages | 516-32 |
| PubMed ID | 25227985 | Mgi Jnum | J:262443 |
| Mgi Id | MGI:6163080 | Doi | 10.1038/mi.2014.85 |
| Citation | Platzer B, et al. (2015) Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites. Mucosal Immunol 8(3):516-32 |
| abstractText | Antigen-mediated cross-linking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcvarepsilonRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcvarepsilonRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcvarepsilonRI signals for DC function remain poorly understood. We show that humanized mice that express FcvarepsilonRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcvarepsilonRI cross-linking fails to induce maturation or production of inflammatory mediators in human DCs and FcvarepsilonRI-humanized DCs. Furthermore, conferring expression of FcvarepsilonRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcvarepsilonRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcvarepsilonRI 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 FcvarepsilonRI-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. |
