Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis

Authors: CORTESA, LIZETTE - North Carolina State University; BRODSKY, DAVID - North Carolina State University; Chen, Celine; PRIDGEN, TIFFANY - North Carolina State University; ODLE, JACK - North Carolina State University; SNYDER, DOUG - North Carolina State University; CRUSE, GLENN - North Carolina State University; PUTIKOVA, ARINA - Mayo Clinic College Of Medicine; MASUDA, MIA - Mayo Clinic College Of Medicine; DOYLE, ALFRED - Mayo Clinic College Of Medicine; WRIGHT, BENJAMIN - Mayo Clinic College Of Medicine; Dawson, Harry; BLIKSLAGER, ANTHONY - North Carolina State University; DELLON, EVAN - University Of North Carolina; LASTER, SCOTT - North Carolina State University; KASER, TOBIAS - North Carolina State University

Submitted to: Frontiers in Allergy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2022
Publication Date: 11/14/2022
Citation: Cortesa, L.M., Brodsky, D., Chen, C.T., Pridgen, T., Odle, J., Snyder, D., Cruse, G., Putikova, A., Masuda, M.Y., Doyle, A.D., Wright, B.L., Dawson, H.D., Blikslager, A., Dellon, E.S., Laster, S.M., Kaser, T. 2022. Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis. Frontiers in Allergy. 3:2022. https://doi.org//10.3389/falgy.2022.1029184.
DOI: https://doi.org/10.3389/falgy.2022.1029184

Interpretive Summary: Food allergy affects ~8% of the world’s population and is caused by excessive immune responses against food allergens. Rodent models have only been partial effective in food allergy modeling because of difference from humans, in their immune response. To address this, we developed a swine model to not only induce food allergy but also monitor the pathological changes and underlying immune mechanisms. With the high biological relevance of pigs, this model can be used to propel basic, translational, and applied research on food allergy. On the example of the food allergy eosinophilic esophagitis, we follow the induction of a systemic immune response leading to food allergy in the esophagus. In the future, this model will be used to study existing and develop new pre- and intervention strategies for food allergy.

Technical Abstract: Eosinophilic esophagitis (EoE) is an important food allergy with increasing incident rates. EoE affects both children and adults and leads to pain, a failure to thrive, and food bolus obstructions. Despite EoE’s strong impact on human health and welfare, there are no FDA-approved treatments for EoE. To facilitate the development of EoE treatment options, goal of this study was to establish swine as a relevant large animal model for translational biomedical research on EoE. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia – a hallmark of human EoE. In this study, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces i) a systemic T-helper 2 and IgE response, ii) a local expression of eotaxin-1 and other allergy-related immune markers, iii) esophageal eosinophilia (>15 eosinophils/0.24mm2), iv) and both linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop the urgently needed intervention strategies for EoE.