CD23 provides a non-inflammatory pathway for IgE-allergen complexes.

Engeroff, Paul; Caviezel, Flurin; Müller, David; Thoms, Franziska; Bachmann, Martin F.; Vogel, Monique (2020). CD23 provides a non-inflammatory pathway for IgE-allergen complexes. Journal of allergy and clinical immunology, 145(1), 301-311.e4. Elsevier 10.1016/j.jaci.2019.07.045

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BACKGROUND Type I hypersensitivity is mediated by allergen-specific IgE which sensitizes the high-affinity IgE receptor FcεRI on mast cells and basophils which drive allergic inflammation upon secondary allergen contact. CD23/FcεRII, 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 FcεRI and CD23 is blocked by reciprocal allosteric inhibition suggesting that the two receptors exert distinct roles in IgE handling. OBJECTIVE We aimed to study how free IgE versus pre-complexed IgE-allergen immune complexes (IgE-ICs) target the two IgE receptors FcεRI and CD23 and we investigated the functional implications of the two 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 FcεRI preferentially binds free IgE while CD23 preferentially binds IgE-ICs. We further show that those different binding properties directly translate to distinct biological functions: free IgE initiates allergic inflammation via FcεRI on allergic effector cells while IgE-ICs are non-inflamatory due to reduced FcεRI binding and enhanced, CD23-dependent serum clearance. CONCLUSION We propose that IgE-ICs are non-inflammatory through reduced engagement by FcεRI but increased targeting of the CD23 pathway.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Engeroff, Paul Simon; Müller, David; Bachmann, Martin and Vogel, Monique

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

15 Nov 2019 16:13

Last Modified:

10 Jan 2020 01:32

Publisher DOI:

10.1016/j.jaci.2019.07.045

PubMed ID:

31437490

Uncontrolled Keywords:

CD23 FcεRI IgE clearance IgE sensitization IgE-allergen complex inflammation

BORIS DOI:

10.7892/boris.135087

URI:

https://boris.unibe.ch/id/eprint/135087

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