phaidra.vetmeduni.ac.at o:3492 DOI 10.1111/all.16181 Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice 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.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.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.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. eng Alternaria Alternata; Fungal Allergy; Immunomodulation; Retinoic Acid; Vitamin A 2024-09-06T09:38:47.351Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Fakhimahmadi;Aila; FN:Aila Fakhimahmadi X-ORCID:https://orcid.org/0000-0002-6804-6238 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hufnagl;Karin; FN:Karin Hufnagl X-ORCID:https://orcid.org/0000-0002-2288-2468 END:VCARD BEGIN:VCARD VERSION:3.0 N:Jensen-Jarolim;Erika; FN:Erika Jensen-Jarolim X-ORCID:https://orcid.org/0000-0003-4019-5765 END:VCARD BEGIN:VCARD VERSION:3.0 N:Pali-Schöll;Isabella; FN:Isabella Pali-Schöll X-ORCID:https://orcid.org/0000-0003-2089-6011 END:VCARD BEGIN:VCARD VERSION:3.0 N:Roth-Walter;Franziska; FN:Franziska Roth-Walter X-ORCID:https://orcid.org/0000-0001-5005-9228 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hofstetter;Gerlinde; FN:Gerlinde Hofstetter X-ORCID:https://orcid.org/0000-0003-2077-4479 END:VCARD BEGIN:VCARD VERSION:3.0 N:Wiederstein;Markus; FN:Markus Wiederstein X-ORCID:https://orcid.org/0000-0002-4750-4746 END:VCARD BEGIN:VCARD VERSION:3.0 N:Jensen;Sebastian A.; FN:Sebastian A. Jensen X-ORCID:https://orcid.org/0000-0002-6216-193X END:VCARD BEGIN:VCARD VERSION:3.0 N:Berger;Markus; FN:Markus Berger END:VCARD BEGIN:VCARD VERSION:3.0 N:Szepannek;Nathalie; FN:Nathalie Szepannek END:VCARD BEGIN:VCARD VERSION:3.0 N:Bianchini;Rodolfo; FN:Rodolfo Bianchini X-ORCID:https://orcid.org/0000-0003-0351-6937 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by-nc/4.0 application/pdf 19113881 https://phaidra.vetmeduni.ac.at/o:3492 https://phaidra.vetmeduni.ac.at/api/object/o:3492/thumbnail LOMv1.0 discipline