**3. Pathogenesis**

Exposure of the esophagus to food and aeroallergens in genetically predisposed individuals may initiate the process of eosinophilic esophagitis although the exact mechanism is currently unknown [5]. Foods most commonly implicated in EoE are: Milk, egg, wheat, soy, peanuts, beans, rye and beef. Genomewide association analysis (GWAS) suggested that CAPN14 at 2p23 locus is upregulated after epithelial exposure to interleukin (IL)13 [6]. Recently, epithelialderived cytokine thymic stromal lymphopoietin (*TSLP*) gene at 5q22 locus has been identified as a candidate gene in

**Figure 1.** *Pathogenesis of EoE.*

#### *Eosinophilic Esophagitis in 2021 DOI: http://dx.doi.org/10.5772/intechopen.97166*

a multicenter GWAS. There is an increased expression of TSLP in patients with EoE. TSLP activates dendritic cells (antigen presenting cells). Food allergen is initially recognized by antigen presenting cells which differentiate CD4 cells into TH1 cells and TH2 cells. TH1 cells secrete interferonγ (IFN-Υ) and transforming growth factorβ (TGF-β). TH2 cells secrete IL4, IL5 and IL13. There is also single nucleotide polymorphism (SNP) in this TSLP receptor gene in male patients with EoE. This gene is found on the pseudoautosomal region on Xp22.3 and Yp11.3. This finding may explain increased prevalence of EoE in male patients. There is also a suggestion of second hit for the development of EoE. Tolllike receptor3 (TLR3) can recognize doublestranded RNA (found in some viruses) and can induce TSLP [7]. IL5 is responsible for eosinophilic infiltration, growth and survival. Eosinophils secrete various inflammatory cytokines and chemokines including macrophage migration inhibitory factor (MMIF), tumor necrosis factor (TNF), granulocytemonocyte colony stimulating factors (GMCSF) and toxic granules [8]. TGF-β1 is a profibrotic molecule and helps in remodeling of the esophagus in EoE. This may lead to esophageal luminal narrowing, stricture formation and dysmotility. Eotaxin3 is a strong chemotactic agent for esophageal eosinophilia. A single nucleotide polymorphism in the human *eotaxin-3* gene was associated with disease susceptibility. IL4 and IL13 secreted by TH2 can stimulate eotaxin3. In telomeraseimmortalized esophageal squamous cells of EoE patients, IL4 stimulated eotaxin3 secretion was blocked by PPI omeprazole and lansoprazole [9]. This may explain PPI responsiveness of esophageal eosinophilia. Twin and family studies suggest that there is not only increased prevalence of EoE in male sex but also in monozygotic twins and other family member [10]. The pathogenesis of EoE is shown in a flow diagram in **Figure 1**.
