Local type 2 immunity in eosinophilic gastritis

Background: Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied. Objective: We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology. Methods: Gastric biopsy samples (n = 6 EoG, n = 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n = 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters. Results: Gastric biopsy samples contained CD3(+) T cells that were mainly CD8(+); the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7 +/- 3.0 and 4.3 +/- 0.6, respectively; P =.28). Gastric regulatory T (CD3(+) CD4(+) FOXP3(+)) and T-H(2) (CD3(+)CD4(+)GATA3(+)) cell levels were increased in EoG versus controls (2-fold, P <.05 and 10-fold, P <.001, respectively) and correlated with gastric eosinophil levels (r 5 0.63, P <.05 and r 5 0.85, P <.001, respectively), endoscopic pathology (r = 0.56, P <.01; r = 0.84, P <.001, respectively), and histopathology (r = 0.72, P <.01; r = 0.82, P <.01, respectively). Cytokinepositive, most notably IL-4(+), T-H(2) cell levels strongly correlated with histologic and endoscopic scores (r = 0.82, P <.0001 and r = 0.78, P <.0001, respectively). In an independent EoG cohort (n = 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r = 0.22, P <.005; r = 0.54, P <.0001; and r = 0.36, P <.0001, respectively) and endoscopic score (r = 0.27, P <.001; r = 0.40, P <.0001; and r = 0.35, P <.0001, respectively). Conclusions: EoG is a T-H(2) cell-associated disease featuring increased gastric type 2 cytokine-producing CD3(+)CD4(+) GATA3(+)T(H)(2) cells that strongly correlate with disease pathologies.

Automated summary

This study examines the correlation between T cell populations in the stomach and the pathology of eosinophilic gastritis (EoG). The results show that EoG is associated with increased levels of gastric T-H(2) cells and cytokine production. Specifically, IL-4 levels in T-H(2) cells strongly correlate with the severity of histologic and endoscopic EoG scores. The findings suggest that EoG is a T-H(2) cell-associated disease, and T-H(2) cells play an important role in its pathology.