Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens Is Associated With IL-4/IL-13 and CCL11 but Not Ige in Genetic Susceptible Mice

Authors

Anish Maskey, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA.Follow
Kamal Srivastava, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA.Follow
Gary Soffer, Department of Allergy and Immunology, Yale University, New Haven, CT, USA.
David Dunkin, Division of Pediatric Gastroenterology and Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Qian Yuan, Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Boston, MA, USA.
Xiu-Min Li, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA.Follow

Author Type(s)

Faculty

DOI

10.2147/JIR.S372449

Journal Title

Journal of Inflammation Research

First Page

5527

Last Page

5540

Document Type

Article

Publication Date

1-1-2022

Department

Pathology, Microbiology and Immunology

Abstract

BACKGROUND: Eosinophilic Esophagitis (EoE) is an increasingly common chronic inflammatory disease. The pathological mechanisms underlying EoE are largely unknown. OBJECTIVE: We sought to understand the mechanisms underlying aeroallergen-induced EoE in Sharpin gene deficient (Sharpin-/-) mice that is prone to inflammatory response. METHODS: Sharpin-/-mice were exposed with and ovalbumin intranasally every alternate day for 4 weeks. Wild type (WT) naïve mice, WT exposed, and un-exposed Sharpin-/- mice were controls. Histopathological analysis was performed by H&E, trichrome and major basic protein staining. Total and specific IgE, IgG, and IgA levels were measured by ELISA and Th2 cytokine and CCL11 chemokine gene expression were determined. RESULTS: Airborne allergen exposed Sharpin-/- mice showed severe eosinophilic inflammation in the esophagus (p < 0.001), and markedly increased epithelial thickening (p < 0.0001) compared to WT normal controls, whereas airborne allergen exposed WT mice and unexposed Sharpin-/- mice only showed mild eosinophilic inflammation in the esophagus. These exposed Sharpin-/- mice also showed over 7-fold increase in blood eosinophils (p < 0.0001), 60-fold increase in eosinophils in bronchoalveolar lavage fluid (p < 0.0001) and 4-fold increase in eosinophils in the skin (p < 0.0001) compared to normal controls. Surprisingly, exposed Sharpin-/- mice did not show elevation of serum total or antigen-specific IgE levels but reduced total IgA and IgG levels than normal controls There was a marked increase in IL-4, IL-13 and CCL11 gene expression in esophageal tissue (p < 0.001) in exposed Sharpin-/- mice compared to WT normal mice. CONCLUSION: Th2 cytokines and chemokines, but not IgE may play an important pathologic role in aeroallergen-induced EoE. This study may provide insight into new therapeutics for EoE.

Recommended Citation

Maskey, A., Srivastava, K., Soffer, G., Dunkin, D., Yuan, Q., & Li, X. (2022). Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens Is Associated With IL-4/IL-13 and CCL11 but Not Ige in Genetic Susceptible Mice. Journal of Inflammation Research, 15, 5527-5540. https://doi.org/10.2147/JIR.S372449