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Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice.
- Source :
-
Allergy [Allergy] 2024 Aug; Vol. 79 (8), pp. 2144-2156. Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
-
Abstract
- Background: We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo.<br />Methods: Alt a 1-RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria-allergic donors were stimulated with Alt a 1 complexed with RA (holo-Alt a 1) or empty apo-Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE-binding and crosslinking assays to apo- and holo-protein were correlated to B-cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo-Alt a 1, holo-Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression.<br />Results: In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo-Alt a 1 loaded with RA reduced IL-13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B-cell epitopes and reduced its IgE-binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo-Alt a 1, but not of apo-Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen-presenting cells and induced IL-10 production.<br />Conclusion: Holo-Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen-specific immunotherapy in Alternaria allergy.<br /> (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Mice
Female
Humans
Hypersensitivity immunology
Fungal Proteins immunology
Th2 Cells immunology
Th2 Cells metabolism
Mice, Inbred BALB C
Allergens immunology
Alternaria immunology
Tretinoin pharmacology
Immunoglobulin E immunology
Disease Models, Animal
Cytokines metabolism
Antigens, Fungal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1398-9995
- Volume :
- 79
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Allergy
- Publication Type :
- Academic Journal
- Accession number :
- 38818808
- Full Text :
- https://doi.org/10.1111/all.16181