Fig. 4. Food allergen as a promoter in eosinophilic esophagitis (EoE) pathogenesis. Notwithstanding with the history of genetic disposition or gastrointestinal disease, exposure to oral food allergen would promote the epithelial barrier disruption and affect the healthy balance of body microbiota in EoE subjects. Food allergens could then infiltrate also through the skin, engage to pathogen-related receptors and drive epithelial cells activation to pro-inflammatory cytokines generation which are responsible for the trafficking of the inflammatory cells. Under epithelial injury condition, thymic stromal lymphopoietin (TSLP) generation is provoked from epithelial cells. TSLP stimulates basophils to generate interleukin (IL)-4 which support allergic sensitization after allergen being presented to a naive T cell, driving allergen-specific Th2 cells activation. Adequate allergen challenges facilitate Th2 cells recruitment and expansion, secreting vast IL-5 and IL-13 which are crucial in eosinophils trafficking and tissue remodeling. Th2 cells locally promote class switching of B cells to produce antigen-specific IgE, which binds to the surface of mast cells and produce antigen-specific IgG which engage to the surface of basophils. Activation of mast cells and basophils leads to the release of pro-inflammatory mediators such as transforming growth factor beta (TGF-β), which contributes to the local inflammatory responses and promotes remodeling and enhances muscle cell contractility. Antigen presenting cell capturing food allergens would subsequently migrate to the regional lymph nodes and thus mediating food-specific T cells activation. Food proteins may induce T-cell responses either as a consequence of antigen presentation by dendritic cells (DCs) or directly with subsequent eosinophil activation. By releasing toxic granule proteins and cytokines, eosinophils defend against invading pathogens, but cause tissue damage, stimulating fibrosis and perpetuating inflammation. In addition, fibroblasts overexpress periostin and downregulate filaggrin likely in response to IL-13. Eotaxin-3 and periostin overexpression cooperatively chemoattract CCR3 positive cells, a process primed by IL-5 which regulates eosinophil responsiveness to eotaxins and the circulating level of eosinophils. The pathomechanisms of EoE overlapping with multiple inflammatory cells are indicated. TNF, tumor necrosis factor; NKT, natural killer T.