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Abstract
Food allergy is a growing global public health concern. As treatment strategies are currently limited to allergen avoidance and emergency interventions, there is an increasing demand for appropriate models of food allergy for the development of new therapeutics. Many models of food allergy rely heavily on the use of animals, and while useful, many are unable to accurately reflect the human system. In order to bridge the gap between in vivo animal models and clinical trials with human patients, human models of food allergy are of great importance. This review will summarize the commonly used human ex vivo and in vitro models of food allergy and highlight their advantages and limitations regarding how accurately they represent the human in vivo system. We will cover biopsy-based systems, precision cut organ slices, and coculture systems as well as organoids and organ-on-a-chip. The availability of appropriate experimental models will allow us to move forward in the field of food allergy research, to search for effective treatment options and to further explore the cause and progression of this disorder.
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Fig. 1.
Schematic of allergic sensitization and re-exposure. Sensitization: Food allergens can cross the luminal barrier by transcellular or paracellular transport, or through direct luminal antigen sampling by dendritic cells (DCs). These allergens are picked up and processed by DCs which can then migrate to mesenteric lymph nodes (MLN) and present the allergen to naïve CD4+ T cells in the context of MHC II. These T cells can then differentiate into Th2 cells that secrete pro-allergic cytokines that influence B cells to become IgE secreting plasma cells. These allergen-specific IgE antibodies can then bind to the Fcε RI (high affinity IgE receptor) expressed on the main effector cells of the allergic response, including mast cells and basophils. Re-sensitization: Upon re-exposure to the allergen, the allergen-specific IgE on the surface of the effector cells can bind, crosslink and activate the cell leading to degranulation of pro-inflammatory mediators. The release of these factors can cause multiple downstream effects and result in the recruitment of other inflammatory cell subsets. APC, antigen-presenting cell; IL, interleukin; MHC, major histocompatibility complex; LTC4, leukotriene C4; LTB4, leukotriene B4; LTE, leukotriene E; PDG D2, prostaglandin D2; PAF, platelet-activating factor.
Fig. 2.
Human in vitro and ex vivo models for food allergy research. Different types of human tissue and cell-based models potentially used to study food allergy in order of proximity to the human system. (A) In vitro coculture systems utilize Transwell inserts on which epithelial cells are cultured and allowed to polarize. Immune cells can be preloaded into the wells to examine cellular interactions. (B) Lung-on-a chip models consist of a membrane on which human lung epithelial cells line the top and are separated from human blood cells that line the bottom. Air flows over the epithelial cells and fluid that mimics blood flows along the bottom creating an environment reflective of the human lung. Vacuum channels on either side allow the cells to be stretched gently mimicking the mechanical movements of breathing. (C) Organoids can be generated using gut samples from human donors, the crypts are then isolated and used to form mini-gut cultures [57]. (D) Precision cut organ slices require the formation of tissue cores from agarose filled organs that are then cut into thin slices of fixed thickness. These slices are then incubated and used for experimentation. (E) Biopsy based models utilize tissue directly extracted from the organ of interest which is subsequently cultured and used for experimentation.
Table 1.
Comparison of the different human in vitro and ex vivo models of food allergy
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