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Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity
- Source :
- Antioxidants, 12(1). MDPI Multidisciplinary Digital Publishing Institute, Antioxidants; Volume 12; Issue 1; Pages: 42
- Publication Year :
- 2023
-
Abstract
- 16 Pág.<br />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.<br />The study was partly supported by Biomedical Int. R+D GmbH, Vienna, Austria and by Bencard Allergy GmbH, Munich, Germany. A.F. and K.H. were supported by the Danube Allergy Research Cluster-DARC #08 of the Karl-Landsteiner University, Krems, Austria, to E.J.-J.
- Subjects :
- immune resilience
Salicylic-Acid
Receptor
Activation
Protein
Deficiency
Ige
Inhibition
Flavonoids
Mechanism
Immunity
Physiology
holo-Bet v 1
major allergen
immunomodulation
iron
quercetin
birch pollen
pathogenesis-related proteins
innate defense
nutritional immunity
Clinical Biochemistry
Cell Biology
Biochemistry
Molecular Biology
Food Science
Subjects
Details
- Language :
- English
- ISSN :
- 20763921
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Antioxidants
- Accession number :
- edsair.doi.dedup.....cb00fbce482c7b48c2b297c06ae8d472