Evaluating Changes in T Cell Composition and Gene Expression in Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic inflammation of the esophagus, yet the roles of individual T cell subsets throughout disease progression remain incompletely understood. This study investigated changes in T cell composition and gene expression across Active EoE, Remission, and healthy Control esophageal tissue biopsies using single-cell RNA sequencing (scRNA-seq) data from 71,342 T cells representing 14 distinct T-cell subtypes (Ding et al., 2024). Cellular composition was evaluated using subtype abundance and enrichment analyses [CITE], while differential gene expression was analyzed through pairwise disease-state comparisons followed by protein-protein interaction (PPI) network [CITE] and MCODE [CITE] cluster analyses to identify biologically relevant pathways. Active EoE demonstrated more than a twofold increase in total T cell abundance compared with Remission and Control samples. Th2 cells were strongly enriched in Active disease, whereas Th17 and CD4+ tissue-resident memory (TRM) cells were significantly depleted in both Active and Remission states, indicating that immune dysregulation persists despite clinical remission. Additional analyses identified altered RNA splicing pathways and increased MHC II antigen presentation within CD8+ effector T cells during Active disease, implicating persistent antigen-driven immune activation. Together, these findings demonstrate that remission does not represent a complete return to a healthy immunologic state and reveal persistent alterations in T cell composition and function that may contribute to disease recurrence. These results highlight the importance of deeper immune profiling and identify potential cellular and molecular targets for future therapeutic investigation.