دورية أكاديمية
أعرض في EDS

Cow's milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells.

التفاصيل البيبلوغرافية
العنوان: Cow's milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells.
المؤلفون: Roth-Walter F; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: franziska.roth-walter@meduniwien.ac.at., Afify SM; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Laboratory Medicine and Immunology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt., Pacios LF; Biotechnology Department, ETSIAAB, Center for Plant Biotechnology and Genomics, CBGP (UPM-INIA), Technical University of Madrid, Madrid, Spain., Blokhuis BR; Faculty of Science, Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Redegeld F; Faculty of Science, Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Regner A; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria., Petje LM; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria., Fiocchi A; Childrens Hospital Bambino Gesù, Rome, Italy., Untersmayr E; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Dvorak Z; Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic., Hufnagl K; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Pali-Schöll I; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Jensen-Jarolim E; The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: erika.jensen-jarolim@medunwien.ac.at.
المصدر: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2021 Jan; Vol. 147 (1), pp. 321-334.e4. Date of Electronic Publication: 2020 May 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: St Louis, Mosby.
مواضيع طبية MeSH: Iron*/chemistry , Iron*/pharmacokinetics , Iron*/pharmacology , Lactoglobulins*/chemistry , Lactoglobulins*/pharmacokinetics , Lactoglobulins*/pharmacology, Leukocytes, Mononuclear/*immunology , Mast Cells/*immunology , Milk/*chemistry , Milk Hypersensitivity/*immunology, Animals ; Cattle ; Humans ; Mice ; Mice, Inbred BALB C ; Milk Hypersensitivity/drug therapy
مستخلص: Background: Beta-lactoglobulin (BLG) is a bovine lipocalin in milk with an innate defense function. The circumstances under which BLG is associated with tolerance of or allergy to milk are not understood.
Objective: Our aims were to assess the capacity of ligand-free apoBLG versus loaded BLG (holoBLG) to protect mice against allergy by using an iron-quercetin complex as an exemplary ligand and to study the molecular mechanisms of this protection.
Methods: Binding of iron-quercetin to BLG was modeled and confirmed by spectroscopy and docking calculations. Serum IgE binding to apoBLG and holoBLG in children allergic to milk and children tolerant of milk was assessed. Mice were intranasally treated with apoBLG versus holoBLG and analyzed immunologically after systemic challenge. Aryl hydrocarbon receptor (AhR) activation was evaluated with reporter cells and Cyp1A1 expression. Treated human PBMCs and human mast cells were assessed by fluorescence-activated cell sorting and degranulation, respectively.
Results: Modeling predicted masking of major IgE and T-cell epitopes of BLG by ligand binding. In line with this modeling, IgE binding in children allergic to milk was reduced toward holoBLG, which also impaired degranulation of mast cells. In mice, only treatments with holoBLG prevented allergic sensitization and anaphylaxis, while sustaining regulatory T cells. BLG facilitated quercetin-dependent AhR activation and, downstream of AhR, lung Cyp1A1 expression. HoloBLG shuttled iron into monocytic cells and impaired their antigen presentation.
Conclusion: The cargo of holoBLG is decisive in preventing allergy in vivo. BLG without cargo acted as an allergen in vivo and further primed human mast cells for degranulation in an antigen-independent fashion. Our data provide a mechanistic explanation why the same proteins can act either as tolerogens or as allergens.
(Copyright © 2020. Published by Elsevier Inc.)
فهرسة مساهمة: Keywords: Allergen; BLG; Bos d 5; allergy; cow's milk; iron; ligand; lipocalin; milk; quercetin; tolerance; β-lactoglobulin
المشرفين على المادة: 0 (Lactoglobulins)
E1UOL152H7 (Iron)
تواريخ الأحداث: Date Created: 20200603 Date Completed: 20210726 Latest Revision: 20210726
رمز التحديث: 20240628
DOI: 10.1016/j.jaci.2020.05.023
PMID: 32485264
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-6825
DOI:10.1016/j.jaci.2020.05.023