Researchers at Children’s Hospital of Philadelphia (CHOP) identified a potential new therapeutic target for eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease of the esophagus. The findings were published today in the journal Gut.
EoE is characterized by esophageal epithelial remodeling, barrier dysfunction and inflammation. While some patients can achieve remission with proper treatment, molecular and structural changes to the epithelium – in this case, the layer of cells found on the surface of the esophagus – caused by the disease can persist and contribute to ongoing symptoms and eventual 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 senior study author Amanda Muir, MD, a pediatric gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition at CHOP. “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.”
Prior studies found that the transcription factor FOXM1 is a key regulator of epithelial proliferation and inflammation in allergic asthma, another chronic disease involving inflammation. Since transcription factors often regulate the transcription of many genes that could be involved in a variety of diseases, researchers wanted to study in further detail whether FOXM1 was implicated in EoE and whether it could serve as a therapeutic target.
The researchers analyzed FOXM1 expression in human esophageal biopsies, preclinical animal models of EoE and patient-derived organoids – lab-grown mini-esophagi made from human tissue that can be studied outside of the body. These separate analyses allowed the researchers to understand the role of FOXM1 in the esophagus itself and how it relates allergic inflammation.
This study demonstrated that FOXM1 was significantly increased in patients with both active and inactive EoE. When esophageal organoids were exposed to interleukin-13 (IL-13), the major cause of EoE inflammation, FOXM1 expression was increased. In addition, the organoids demonstrated the key signs of epithelial damage in EoE such as barrier integrity loss and basal cell hyperplasia. However, when FOXM1 was inhibited, these changes were reversed in both the organoids and a mouse model of EoE.
“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 study was supported by the National Institutes of Health (NIH) grants R01DK121159, K08AI148456, R01DK124266-01, R01DK138634-01, R01DK135729-01A1, and P30DK050306, and the Children’s Hospital of Philadelphia Gastrointestinal Epithelium Modeling Program.
Sasaki et al, “FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis.” Gut. Online November 20, 2025. DOI: 10.1136/gutjnl-2025-335163.
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Researchers at Children’s Hospital of Philadelphia (CHOP) identified a potential new therapeutic target for eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease of the esophagus. The findings were published today in the journal Gut.
EoE is characterized by esophageal epithelial remodeling, barrier dysfunction and inflammation. While some patients can achieve remission with proper treatment, molecular and structural changes to the epithelium – in this case, the layer of cells found on the surface of the esophagus – caused by the disease can persist and contribute to ongoing symptoms and eventual 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 senior study author Amanda Muir, MD, a pediatric gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition at CHOP. “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.”
Prior studies found that the transcription factor FOXM1 is a key regulator of epithelial proliferation and inflammation in allergic asthma, another chronic disease involving inflammation. Since transcription factors often regulate the transcription of many genes that could be involved in a variety of diseases, researchers wanted to study in further detail whether FOXM1 was implicated in EoE and whether it could serve as a therapeutic target.
The researchers analyzed FOXM1 expression in human esophageal biopsies, preclinical animal models of EoE and patient-derived organoids – lab-grown mini-esophagi made from human tissue that can be studied outside of the body. These separate analyses allowed the researchers to understand the role of FOXM1 in the esophagus itself and how it relates allergic inflammation.
This study demonstrated that FOXM1 was significantly increased in patients with both active and inactive EoE. When esophageal organoids were exposed to interleukin-13 (IL-13), the major cause of EoE inflammation, FOXM1 expression was increased. In addition, the organoids demonstrated the key signs of epithelial damage in EoE such as barrier integrity loss and basal cell hyperplasia. However, when FOXM1 was inhibited, these changes were reversed in both the organoids and a mouse model of EoE.
“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 study was supported by the National Institutes of Health (NIH) grants R01DK121159, K08AI148456, R01DK124266-01, R01DK138634-01, R01DK135729-01A1, and P30DK050306, and the Children’s Hospital of Philadelphia Gastrointestinal Epithelium Modeling Program.
Sasaki et al, “FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis.” Gut. Online November 20, 2025. DOI: 10.1136/gutjnl-2025-335163.
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