An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen
BackgroundThe global demand of sustainable food sources leads to introduction of novel foods on the market, which may pose a risk of inducing allergic sensitization. Currently there are no validated in vitro assays mimicking the human mucosal immune system to study sensitizing allergenicity risk of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073034/full |
| _version_ | 1797956802088796160 |
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| author | Marit Zuurveld Cristina Bueno Díaz Frank Redegeld Gert Folkerts Johan Garssen Johan Garssen Belinda van’t Land Belinda van’t Land Linette E.M. Willemsen |
| author_facet | Marit Zuurveld Cristina Bueno Díaz Frank Redegeld Gert Folkerts Johan Garssen Johan Garssen Belinda van’t Land Belinda van’t Land Linette E.M. Willemsen |
| author_sort | Marit Zuurveld |
| collection | DOAJ |
| description | BackgroundThe global demand of sustainable food sources leads to introduction of novel foods on the market, which may pose a risk of inducing allergic sensitization. Currently there are no validated in vitro assays mimicking the human mucosal immune system to study sensitizing allergenicity risk of novel food proteins. The aim of this study was to introduce a series of sequential human epithelial and immune cell cocultures mimicking key immune events after exposure to the common food allergen ovalbumin from intestinal epithelial cell (IEC) activation up to mast cell degranulation.MethodsThis in vitro human mucosal food sensitizing allergenicity model combines crosstalk between IEC and monocyte-derived dendritic cells (moDC), followed by coculture of the primed moDCs with allogenic naïve CD4+ T cells. During subsequent coculture of primed CD4+ T cells with naïve B cells, IgE isotype-switching was monitored and supernatants were added to primary human mast cells to investigate degranulation upon IgE crosslinking. Mediator secretion and surface marker expression of immune cells were determined.ResultsOvalbumin activates IEC and underlying moDCs, both resulting in downstream IgE isotype-switching. However, only direct exposure of moDCs to ovalbumin drives Th2 polarization and a humoral B cell response allowing for IgE mediated mast cell degranulation, IL13 and IL4 release in this sequential DC-T cell-B cell-mast cell model, indicating also an immunomodulatory role for IEC.ConclusionThis in vitro coculture model combines multiple key events involved in allergic sensitization from epithelial cell to mast cell, which can be applied to study the allergic mechanism and sensitizing capacity of proteins. |
| first_indexed | 2024-04-10T23:55:34Z |
| format | Article |
| id | doaj.art-5d2e5dfd5584429cbde675e88d8feb67 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T23:55:34Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5d2e5dfd5584429cbde675e88d8feb672023-01-10T13:56:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10730341073034An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergenMarit Zuurveld0Cristina Bueno Díaz1Frank Redegeld2Gert Folkerts3Johan Garssen4Johan Garssen5Belinda van’t Land6Belinda van’t Land7Linette E.M. Willemsen8Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsChemical Biology and Drug Discovery Group, Department of Pharmacological Sciences, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsImmunology Platform, Danone Nutricia Research B.V., Utrecht, NetherlandsImmunology Platform, Danone Nutricia Research B.V., Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, NetherlandsBackgroundThe global demand of sustainable food sources leads to introduction of novel foods on the market, which may pose a risk of inducing allergic sensitization. Currently there are no validated in vitro assays mimicking the human mucosal immune system to study sensitizing allergenicity risk of novel food proteins. The aim of this study was to introduce a series of sequential human epithelial and immune cell cocultures mimicking key immune events after exposure to the common food allergen ovalbumin from intestinal epithelial cell (IEC) activation up to mast cell degranulation.MethodsThis in vitro human mucosal food sensitizing allergenicity model combines crosstalk between IEC and monocyte-derived dendritic cells (moDC), followed by coculture of the primed moDCs with allogenic naïve CD4+ T cells. During subsequent coculture of primed CD4+ T cells with naïve B cells, IgE isotype-switching was monitored and supernatants were added to primary human mast cells to investigate degranulation upon IgE crosslinking. Mediator secretion and surface marker expression of immune cells were determined.ResultsOvalbumin activates IEC and underlying moDCs, both resulting in downstream IgE isotype-switching. However, only direct exposure of moDCs to ovalbumin drives Th2 polarization and a humoral B cell response allowing for IgE mediated mast cell degranulation, IL13 and IL4 release in this sequential DC-T cell-B cell-mast cell model, indicating also an immunomodulatory role for IEC.ConclusionThis in vitro coculture model combines multiple key events involved in allergic sensitization from epithelial cell to mast cell, which can be applied to study the allergic mechanism and sensitizing capacity of proteins.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073034/fulladvanced in vitro modelallergic sensitizationfood allergymucosal immunityallergenicity risk assessmentovalbumin |
| spellingShingle | Marit Zuurveld Cristina Bueno Díaz Frank Redegeld Gert Folkerts Johan Garssen Johan Garssen Belinda van’t Land Belinda van’t Land Linette E.M. Willemsen An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen Frontiers in Immunology advanced in vitro model allergic sensitization food allergy mucosal immunity allergenicity risk assessment ovalbumin |
| title | An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen |
| title_full | An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen |
| title_fullStr | An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen |
| title_full_unstemmed | An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen |
| title_short | An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen |
| title_sort | advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk a proof of concept using ovalbumin as model allergen |
| topic | advanced in vitro model allergic sensitization food allergy mucosal immunity allergenicity risk assessment ovalbumin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073034/full |
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