Food allergen sensitization on a chip: the gut–immune–skin axis

Janssen R, de Kleer JWM, Heming B, Bastiaan-Net S, Garssen J, Willemsen LEM, Masereeuw R. . Trends Biotechnol. 2023 Aug 12:S0167-7799(23)00214-7. 

Highlights

• Food allergen sensitization is characterized by a type 2 immune response towards a specific food protein and can adversely affect the patient after re-exposure of this food allergen.
• The gut, skin, and lymph nodes (including immune cells) are interconnected key organs in food allergen sensitization.
• Gut and skin organ-on-a-chip (OoC) devices have been developed with an immune component to recapitulate the 3D epithelial cell–immune cell crosstalk, although specialized gut–immune–skin OoC models to study food protein sensitizing allergenicity capacity are not available yet.
• The inclusion of compartmentalized innate and adaptive immune cells is crucial to mimic the immune cascade in the gut–immune–skin axis in a stepwise manner.
• Engineering a gut–immune–skin axis OoC can better evaluate food allergen sensitization in the future and advance mechanistic insight.

Abstract

The global population is growing, rapidly increasing the demand for sustainable, novel, and safe food proteins with minimal risks of food allergy. In vitro testing of allergy-sensitizing capacity is predominantly based on 2D assays. However, these lack the 3D environment and crosstalk between the gut, skin, and immune cells essential for allergy prediction. Organ-on-a-chip (OoC) technologies are promising to study type 2 immune activation required for sensitization, initiated in the small intestine or skin, in interlinked systems. Increasing the mechanistic understanding and, moreover, finding new strategies to study interorgan communication is of importance to recapitulate food allergen sensitization in vitro. Here, we outline recently developed OoC platforms and discuss the features needed for reliable prediction of sensitizing allergenicity of proteins.

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