| First Author | Engeroff P | Year | 2020 |
| Journal | J Allergy Clin Immunol | Volume | 145 |
| Issue | 1 | Pages | 301-311.e4 |
| PubMed ID | 31437490 | Mgi Jnum | J:293513 |
| Mgi Id | MGI:6452883 | Doi | 10.1016/j.jaci.2019.07.045 |
| Citation | Engeroff P, et al. (2020) CD23 provides a noninflammatory pathway for IgE-allergen complexes. J Allergy Clin Immunol 145(1):301-311.e4 |
| abstractText | BACKGROUND: Type I hypersensitivity is mediated by allergen-specific IgE, which sensitizes the high-affinity IgE receptor FcepsilonRI on mast cells and basophils and drives allergic inflammation upon secondary allergen contact. CD23/FcepsilonRII, 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 FcepsilonRI 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 FcepsilonRI 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 FcepsilonRI 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 FcepsilonRI on allergic effector cells, while IgE-ICs were noninflammatory because of reduced FcepsilonRI binding and enhanced CD23-dependent serum clearance. CONCLUSION: We propose that IgE-ICs are noninflammatory through reduced engagement by FcepsilonRI but increased targeting of the CD23 pathway. |
