A new study from the Gray Faculty of Medical and Health Sciences at Tel Aviv University may mark a breakthrough in the treatment of Eosinophilic Esophagitis (EoE) - a chronic inflammatory disease of the esophagus caused by food allergies. EoE leads to difficulty swallowing, chest and abdominal pain, and even growth delays in children. Its prevalence has been steadily increasing over the past decade in Israel and the Western world.
In this study, researchers identified the protein TSLP as a trigger for the disease's development, and found that neutralizing it may significantly ease symptoms.
The study, led by Prof. Ariel Munitz and doctoral student Anish Dsilva from the Gray Faculty of Medical and Health Sciences, was conducted in collaboration with Dr. Chen Varol of Ichilov Hospital, Prof. Marc Rothenberg of Cincinnati Children's Hospital, and the pharmaceutical company AstraZeneca. It was supported by grants from the Israel Science Foundation, the US-Israel Binational Science Foundation, and the Azrieli Foundation Canada-Israel. The article was published in Allergy, the leading journal in clinical immunology.
Understanding the Disease
Prof. Munitz explains: "Eosinophilic Esophagitis, or EoE, is a type of food allergy. It is a chronic inflammation of the esophagus caused by an abnormal immune response to food - mainly milk, eggs, wheat, nuts, fish, and more. The disease is characterized by an accumulation of eosinophils, a type of white blood cell that is not typically present in a healthy esophagus. EoE is often associated with other allergic conditions such as asthma and atopic dermatitis. It causes difficulty swallowing, food getting stuck in the esophagus, chest and abdominal pain, and growth delays in children. Current treatments require restrictive diets, and in severe cases, patients rely on essential amino acid formulas. Over the past decade, there has been a concerning rise in the prevalence of EoE worldwide, including in Israel. We are studying the disease in depth to understand the involvement of various immune system components in its progression. These components may serve as targets for future treatment for this disease, and for other allergic disorders as well."
A previous study from Prof. Munitz's lab, also published in Allergy, presented an experimental model that closely mimics the course and symptoms of EoE in humans. As a direct continuation of that study, the researchers now focused on a specific aspect of the disease, aiming to understand the role of epithelial cells. Prof. Munitz elaborates: "Epithelial cells form a protective outer layer that prevents foreign bodies from entering organs, including the digestive and respiratory systems. In allergic conditions, epithelial cells release various substances in response to encountering an allergen, and these substances trigger the chain of events that initiate the inflammatory process we experience as an allergy attack."
TSLP: The Central Player
The researchers found that epithelial cells in the esophagus of the EoE experimental model secreted high levels of two proteins: IL-33 and TSLP. They also discovered that the esophageal tissue contained immune cells with receptors for both proteins, indicating that these are active proteins capable of initiating the disease.
They then examined whether each protein had a distinct role or acted together. Using genetic engineering, they created models lacking one of the proteins.
The results were clear: removing IL-33 did not change the disease course, but removing TSLP led to a dramatic improvement - in some cases preventing the disease entirely. Similarly, neutralizing TSLP with an antibody caused a significant reduction in symptoms. Sequencing and bioinformatic analyses confirmed that TSLP acts as a master regulator of EoE, making it a promising therapeutic target.
Prof. Munitz concludes: "In this study, we found that the TSLP protein is a central player in EoE - a disease that causes significant suffering and is becoming increasingly prevalent worldwide. We know that pharmaceutical companies are currently developing a variety of antibodies targeting disease-causing proteins, under the broad category of biological therapies, including antibodies against TSLP. We believe these antibodies could serve as an effective treatment for EoE."
