Cytokine expression in healthy and inflamed mucosa: Probing the role of eosinophils in the digestive tract

Background: In eosinophilic esophagitis (EE), the esophagus is infiltrated with activated eosinophils that often evoke tissue damage, but the intestines of these patients remain unaffected. We thus hypothesized that different tissue‐dwelling eosinophil populations may coexist: activated eosinophils that infiltrate the esophagus and resting eosinophils that reside in unaffected intestines. We sought to characterize different eosinophil subpopulations by comparing the expression of certain proinflammatory proteins in tissue‐dwelling eosinophils at different parts of the gastrointestinal tract. Methods: The 8 patients participating included 6 men and 2 women with a previously confirmed diagnosis of EE, whose average age was 39.4 years (range, 20‐55 yr) and average disease duration was 13.6 years (range, 2‐26 yr). Controls were 3 men and 1 woman, with a mean age of 43.3 years (range, 29‐56 yr) with untreated functional dyspepsia who underwent diagnostic esophagogastroduodenoscopy. Six additional individuals having normal blood eosinophils were recruited for cytokine measurements in blood eosinophils. Immunofluorescence and immunoassays charted expression of CD25 and the TH2 cytokines, interleukin (IL)‐4, IL‐5, IL‐10, and IL‐13, in esophageal, intestinal, and blood eosinophils from controls and patients. Results: Controls showed a small but significant proportion of intestinal, but no blood, eosinophils expressing CD25 and IL‐13, suggesting physiologic activation occurring in the digestive tract. On the other hand, eosinophils infiltrating the inflamed esophageal mucosa of patients with EE showed strong evidence of activation, with most expressing CD25, IL‐4, and IL‐13. Moreover, IL‐13‐positive intestinal eosinophils were increased in patients compared with controls. Conclusions: We thus conclude that tissue‐dwelling eosinophils show different and distinct cytokine expression patterns under noninflammatory and inflammatory conditions.