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Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
Oesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an
Eric M Rodríguez-López1,2,3, Rachel L Clement1,2,3, Megha Lal3
1Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Background:
Eosinophilic oesophagitis (EoE) is a chronic food allergy that causes oesophageal inflammation and dysfunction. Recent work demonstrates IFNγ-dependent gene signatures in inflamed EoE biopsies. IFNγ has been implicated in the promotion of MHCII expression on oesophageal epithelial cells (EECs). However, the regulation of EEC-MHCII expression in vivo, and its contribution to EoE, is unknown.
Objective:
The objective of this study was to determine the regulation and role of EEC-intrinsic MHCII expression in EoE.
Methods:
We examined the expression of HLA II-pathway transcripts in human EECs using single cell RNA-seq datasets and primary human tissues and mouse systems to interrogate the contribution of IFNγ to EEC-MHCII expression. Finally, we used a mouse disease model to test the contribution of epithelial MHCII to food antigen-dependent EoE.
Results:
HLA II transcripts were upregulated in EECs of active EoE patients, compared with controls. Similarly, EEC-MHCII expression was higher in mice with EoE-like inflammation. EEC-MHCII expression was governed by IFNγ-responsive transcriptional regulation. EEC-specific MHCII deficiency resulted in exacerbated eosinophilic inflammation in a model of food antigen-dependent EoE.
Conclusion:
We find a novel immunoregulatory role for IFNγ-dependent EEC-MHCII in the context of oesophageal food allergy.
Clinical Relevance:
Our results expand our understanding of oesophageal immune physiology and identify EEC-MHCII as mediating an anti-inflammatory axis that could be leveraged therapeutically.
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