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 FcɛRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcɛRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcɛRI signals for DC function remain poorly understood. We show that humanized mice that express FcɛRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcɛRI cross-linking fails to induce maturation or production of inflammatory mediators in human DCs and FcɛRI-humanized DCs. Furthermore, conferring expression of FcɛRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcɛRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcɛRI 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 FcɛRI-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.

• Authors: B Platzer, K Baker, M P Vera, K Singer, M Panduro, W S Lexmond, D Turner, S O Vargas, J-P Kinet, D Maurer, R M Baron, R S Blumberg, E Fiebiger
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 8 Issue 3 Pg. 516-32 (May 2015) ISSN: 1935-3456 [Electronic] United States
• PMID: 25227985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Cross-Linking Reagents
• Cytokines
• FcepsilonRI alpha-chain, human
• Lipopolysaccharides
• Receptors, IgE
• Immunoglobulin E
• Ovalbumin
• Papain

Topics

• Allergens (immunology)
• Animals
• Asthma (genetics, immunology, pathology)
• Cell Migration Assays
• Cell Movement (drug effects)
• Cross-Linking Reagents (chemistry)
• Cytokines (biosynthesis, metabolism)
• Dendritic Cells (drug effects, immunology, pathology)
• Egg Hypersensitivity (genetics, immunology, pathology)
• Feedback, Physiological
• Gene Expression Regulation
• Humans
• Immunity, Mucosal
• Immunoglobulin E (chemistry, genetics, immunology)
• Lipopolysaccharides (pharmacology)
• Mast Cells (drug effects, immunology, pathology)
• Mice
• Mice, Transgenic
• Ovalbumin (immunology)
• Papain (pharmacology)
• Primary Cell Culture
• Protein Binding
• Receptors, IgE (chemistry, genetics, immunology)
• Signal Transduction