CD23 provides a noninflammatory pathway for IgE-allergen complexes

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article

Engeroff, Paul^1,2  Caviezel, Flurin^1,2  Mueller, David^1,2  Thoms, Franziska³  Bachmann, Martin F.^1,2,4  Vogel, Monique^1,2 

[1] Univ Hosp Bern, Dept Rheumatol Immunol & Allergol, Bern, Switzerland

[2] Univ Bern, Dept BioMed Res, Bern, Switzerland

[3] Zurich Univ Hosp, Dept Dermatol, Schlieren, Switzerland

[4] Univ Oxford, Jenner Inst, Nuffield Dept Med, Oxford, England

关键词: IgE sensitization;    IgE-allergen complex;    CD23;    Fc epsilon RI;    IgE clearance;    inflammation;   

DOI  :  10.1016/j.jaci.2019.07.045

来源: Elsevier

【 摘 要 】

Background: Type I hypersensitivity is mediated by allergen-specific IgE, which sensitizes the high-affinity IgE receptor Fc epsilon RI on mast cells and basophils and drives allergic inflammation upon secondary allergen contact. CD23/Fc epsilon RII, the low-affinity receptor for IgE, is constitutively expressed on B cells and has been shown to regulate immune responses. Simultaneous binding of IgE to Fc epsilon RI and CD23 is blocked by reciprocal allosteric inhibition, suggesting that the 2 receptors exert distinct roles in IgE handling. Objective: We aimed to study how free IgE versus precomplexed IgE-allergen immune complexes (IgE-ICs) target the 2 IgE receptors Fc epsilon RI and CD23, and we investigated the functional implications of the 2 pathways. Methods: We performed binding and activation assays with human cells in vitro and IgE pharmacokinetics and anaphylaxis experiments in vivo. Results: We demonstrate that Fc epsilon RI preferentially binds free IgE and CD23 preferentially binds IgE-ICs. We further show that those different binding properties directly translate to distinct biological functions: free IgE initiated allergic inflammation through Fc epsilon RI on allergic effector cells, while IgE-ICs were noninflammatory because of reduced Fc epsilon RI binding and enhanced CD23-dependent serum clearance. Conclusion: We propose that IgE-ICs are noninflammatory through reduced engagement by Fc epsilon RI but increased targeting of the CD23 pathway.

【 授权许可】

Free