Eosinophilic esophagitis (EoE)-risk loci contain genes with known roles in the pathoetiology of EoE. Esophageal epithelial cells secrete thymic stromal lymphopoietin (TSLP, encoded by EoE-risk locus 5q22) and interleukin-33 (IL-33) in response to stimuli from various environmental factors. These cytokines act on T-helper cells, leading to their secretion of allergic cytokines including IL-13, IL-4, and IL-5. IL-5 signals primarily through signal transducer and activator of transcription 5 (STAT5) in eosinophils to promote tissue recruitment and survival. IL-13 signals primarily through signal transducer and activator of transcription 6 (STAT6, encoded by EoE-risk locus 12q13) and promotes the transcription of calpain-14 (CAPN14, encoded by EoE-risk locus 2p23) and C-C Motif Chemokine Ligand 26 (CCL26, also known as eotaxin-3). STAT6-dependent IL-13 signaling also leads to decreased expression of the tight junction protein desmoglein 1 (DSG1). Altogether, these signaling pathways lead to eosinophil recruitment and survival, a disrupted esophageal epithelial barrier, and a disorganized esophageal epithelium.