biostudies-literatureRodriguez-Lopez EMIra and Diana RiklisFood Allergy FundAmerican Academy of Allergy Asthma and ImmunologyNIAID NIH HHSNHLBI NIH HHSChildren's Hospital of PhiladelphiaNCI NIH HHSNational Institutes of HealthAmerican Partnership for Eosinophilic DisordersHartwell FoundationNIH HHSThe Hartwell Foundation124-136https://www.ebi.ac.uk/biostudies/studies/S-EPMC12813630biostudies-literatureUnknown56(2)<h4>Background</h4>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.<h4>Objective</h4>The objective of this study was to determine the regulation and role of EEC-intrinsic MHCII expression in EoE.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>We find a novel immunoregulatory role for IFNγ-dependent EEC-MHCII in the context of oesophageal food allergy.<h4>Clinical relevance</h4>Our results expand our understanding of oesophageal immune physiology and identify EEC-MHCII as mediating an anti-inflammatory axis that could be leveraged therapeutically.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical ImmunologyOesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an IFNγ-Dependent Manner.PMC12813630T32 AI055428P30 CA016520T32-AI055428T32‐AI055428R01HL162715R01 HL162715Ruffner MAZhou YCarro SDHill DAGautam RClement RLAssenmacher CAMuir ABRodriguez-Lopez EMBeers JEisenlohr LCLal MSpergel JMfalseOesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an IFNγ-Dependent Manner.<h4>Background</h4>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.<h4>Objective</h4>The objective of this study was to determine the regulation and role of EEC-intrinsic MHCII expression in EoE.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>We find a novel immunoregulatory role for IFNγ-dependent EEC-MHCII in the context of oesophageal food allergy.<h4>Clinical relevance</h4>Our results expand our understanding of oesophageal immune physiology and identify EEC-MHCII as mediating an anti-inflammatory axis that could be leveraged therapeutically.2026-01-01T00:00:00Z2026 Feb2026-07-05T03:12:13.696Z2026-07-05T03:11:08.465ZS-EPMC128136304142942910.1111/cea.70205