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
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.
Human
Comparison of the different human
Biopsy based models | Precision cut organ slices | Coculture systems | Organoids | Organ-on-a-chip | |
---|---|---|---|---|---|
Advantages | · Minimally invasive |
· Generated from otherwise discarded tissue |
· Widely available |
· Comprised of organ specific cell types |
· Simulates 3D structure |
Disadvantages | · Lack of donors |
· Lack of donors |
· Not all relevant cells represented |
· Variability of starter cells |
· Difficult to generate |
Food allergy model | Yes | Yes (lung) | Yes | No | No |