{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:28:31Z","timestamp":1775582911891,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biomedical Int. R+D GmbH, Vienna, Austria and by Bencard Allergy GmbH, Munich, Germany"},{"name":"Danube Allergy Research Cluster-DARC #08 of the Karl-Landsteiner University, Krems, Austria"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/antiox12010042","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:45:54Z","timestamp":1672116354000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity"],"prefix":"10.3390","volume":"12","author":[{"given":"Andreas","family":"Regner","sequence":"first","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Szepannek","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-4746","authenticated-orcid":false,"given":"Markus","family":"Wiederstein","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aila","family":"Fakhimahmadi","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"},{"name":"Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0585-4289","authenticated-orcid":false,"given":"Luis F.","family":"Paciosis","sequence":"additional","affiliation":[{"name":"Center for Plant Biotechnology and Genomics, Biotechnology Department, ETSIAAB, CBGP (UPM-INIA), Universidad Polit\u00e9cnica de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9366-6404","authenticated-orcid":false,"given":"Bart R.","family":"Blokhuis","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8830-7960","authenticated-orcid":false,"given":"Frank A.","family":"Redegeld","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerlinde","family":"Hofstetter","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-3585","authenticated-orcid":false,"given":"Zdenek","family":"Dvorak","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Faculty of Science, Palacky University, 78371 Olomouc, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-5765","authenticated-orcid":false,"given":"Erika","family":"Jensen-Jarolim","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"},{"name":"Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Hufnagl","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"},{"name":"Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5005-9228","authenticated-orcid":false,"given":"Franziska","family":"Roth-Walter","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University of Vienna, 1210 Vienna, Austria"},{"name":"Center of Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/all.12797","article-title":"Structural similarities 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