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Recent work demonstrates IFN\u03b3\u2010dependent gene signatures in inflamed EoE biopsies. IFN\u03b3 has been implicated in the promotion of MHCII expression on oesophageal epithelial cells (EECs). However, the regulation of EEC\u2010MHCII expression in\u00a0vivo, and its contribution to EoE, is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to determine the regulation and role of EEC\u2010intrinsic MHCII expression in EoE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the expression of HLA II\u2010pathway transcripts in human EECs using single cell RNA\u2010seq datasets and primary human tissues and mouse systems to interrogate the contribution of IFN\u03b3 to EEC\u2010MHCII expression. Finally, we used a mouse disease model to test the contribution of epithelial MHCII to food antigen\u2010dependent EoE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HLA II transcripts were upregulated in EECs of active EoE patients, compared with controls. Similarly, EEC\u2010MHCII expression was higher in mice with EoE\u2010like inflammation. EEC\u2010MHCII expression was governed by IFN\u03b3\u2010responsive transcriptional regulation. EEC\u2010specific MHCII deficiency resulted in exacerbated eosinophilic inflammation in a model of food antigen\u2010dependent EoE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We find a novel immunoregulatory role for IFN\u03b3\u2010dependent EEC\u2010MHCII in the context of oesophageal food allergy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>Our results expand our understanding of oesophageal immune physiology and identify EEC\u2010MHCII as mediating an anti\u2010inflammatory axis that could be leveraged therapeutically.<\/jats:p>\n                  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