Researchers at Children’s Hospital of Philadelphia (CHOP) have identified a possible new therapeutic target for eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease affecting the esophagus. The findings were published in the journal Gut.
EoE is marked by changes to the esophageal epithelium, barrier dysfunction, and inflammation. Even when patients achieve remission with treatment, damage to the epithelial layer can persist and lead to ongoing symptoms or relapse.
“Even patients in remission can have epithelial damage, and while the disease might be characterized as inactive, patients can still be negatively impacted by symptoms associated with it,” said Amanda Muir, MD, a pediatric gastroenterologist at CHOP and senior author of the study. “It’s our goal to better understand as many of the underlying causes of eosinophilic esophagitis as possible so that we can work toward therapeutic interventions to correct these issues and improve the quality of life for patients.”
Previous research indicated that FOXM1, a transcription factor, regulates epithelial proliferation and inflammation in allergic asthma. Since transcription factors often influence multiple genes involved in various diseases, CHOP researchers investigated whether FOXM1 plays a role in EoE and if it could be targeted therapeutically.
The team examined FOXM1 expression using human esophageal biopsies, animal models of EoE, and patient-derived organoids—lab-grown mini-esophagi from human tissue. These methods helped clarify FOXM1’s role in allergic inflammation within the esophagus.
Results showed that FOXM1 levels were significantly higher in both active and inactive EoE cases. When organoids were exposed to interleukin-13 (IL-13), which drives EoE inflammation, FOXM1 expression increased along with signs of epithelial damage such as loss of barrier integrity and basal cell hyperplasia. Inhibiting FOXM1 reversed these changes in both organoids and mouse models.
“Not only does this study confirm that FOXM1 plays a critical role in the epithelium, but we also demonstrated how inhibition of FOXM1 represents a promising therapeutic strategy for patients with EoE,” Muir said.
This research received support from several National Institutes of Health grants as well as funding from CHOP’s Gastrointestinal Epithelium Modeling Program.
The full study is titled “FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis” by Sasaki et al., published online November 20, 2025 (DOI: 10.1136/gutjnl-2025-335163).
