An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

Marit Zuurveld*, Cristina Bueno Díaz, Frank Redegeld, Gert Folkerts, Johan Garssen, Belinda van’t Land, Linette E.M. Willemsen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: The 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. Methods: This 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. Results: Ovalbumin 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. Conclusion: This 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.

Original languageEnglish
Article number1073034
Pages (from-to)1-12
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 9 Jan 2023

Keywords

  • advanced in vitro model
  • allergenicity risk assessment
  • allergic sensitization
  • food allergy
  • mucosal immunity
  • ovalbumin

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