Cellular and molecular mediators in EE. Microscopic assessment (lower panel; magnification, ×100) using a tryptase-specific antibody demonstrates scattered mast cells (bright-red-fluorescent cells marked by white arrows) among cytokeratin-positive epithelial cells (green-fluorescent cells, which are appropriately absent from the fibrovascular stroma within a papilla, marked “P”). Two eosinophils are designated by dashed circles. Eosinophils are identified by their characteristic red autofluorescence and nuclear morphology under higher magnification (e.g., lower left cell in top left panel; magnification, ×1000; green channel omitted). Nuclei are fluorescently counterstained (blue) with DAPI. We propose a model of EE pathogenesis involving eotaxin-3 expression by epithelioid cells. Eotaxin-3 overexpression promotes chemoattraction of CCR3-positive eosinophils and expression of the CLC protein. An SNP in the eotaxin-3 gene is associated with EE. Mast cells (white arrows) accumulate in the esophagus, and mast cell genes (tryptase-α and carboxypeptidase A3) are overrepresented in the EE transcript signature (Supplemental Table 5). Eotaxin-3 drives eosinophil activation that leads to tissue damage. CRISP-3, cysteine-rich secretory protein-3.