Title
Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity
Language
English
Description (en)
Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory properties on human immune cells. Binding of Bet v 1 to iron quercetin complexes FeQ2 was determined in docking calculations and by spectroscopy. Serum IgE-binding to Bet v 1 with (holoBet v1) and without ligands (apoBet v 1) were assessed by ELISA, blocking experiments and Western Blot. Crosslinking-capacity of apo/holoBet v 1 were assessed on human mast cells and Arylhydrocarbon receptor (AhR) activation with the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for labile iron and phenotypic changes by flow cytometry. Bet v 1 bound to FeQ2 strongly with calculated Kd values of 1 nm surpassing affinities to quercetin alone nearly by a factor of 1000. Binding to FeQ2 masked IgE epitopes and decreased IgE binding up to 80% and impaired degranulation of sensitized human mast cells. Bet v 1 facilitated the shuttling of quercetin, which activated the anti-inflammatory AhR pathway and increased the labile iron pool of human monocytic cells. The increase of labile iron was associated with an anti-inflammatory phenotype in CD14+monocytes and downregulation of HLADR. To summarize, we reveal for the first time that FeQ2 binding reduces the allergenicity of Bet v 1 due to ligand masking, but also actively contributes anti-inflammatory stimuli to human monocytes, thereby fostering tolerance. Nourishing immune cells with complex iron may thus represent a promising antigen-independent immunotherapeutic approach to improve efficacy in allergen immunotherapy.
Keywords (en)
Salicylic-Acid; Receptor; Activation; Protein; Deficiency; Ige; Inhibition; Flavonoids; Mechanism; Immunity
DOI
10.3390/antiox12010042
Author of the digital object
Andreas Regner (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Franziska Roth-Walter (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Karin Hufnagl (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Erika Jensen-Jarolim (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Zdenek Dvorak (Palacky University)
Gerlinde Hofstetter (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Frank A Redegeld (Utrecht University)
Bart R Blokhuis (Utrecht University)
Luis F Paciosis (Universidad Politécnica de Madrid)
Aila Fakhimahmadi (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Markus Wiederstein (University of Salzburg)
Nathalie Szepannek (University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna)
Format
application/pdf
Size
950.7 kB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Antioxidants
Pages or Volume
16
Volume
12
Number
1
Publisher
MDPI
Publication Date
2023
Citable links
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:1423
https://doi.org/10.3390/antiox12010042
Content
Details
Object type
PDFDocument
Format
application/pdf
Created
14.03.2023 02:05:05
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