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Epithelial Cell-Intrinsic Regulation of Food Antigen-Dependent Eosinophilic Esophagitis Eric M Rodriguez-Lopez
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Rodriguez-Lopez, Eric M., author.
- Language:
- English
- Subjects (All):
- Immunology.
- Cellular biology.
- Molecular biology.
- 0982.
- 0379.
- 0307.
- Local Subjects:
- Immunology.
- Cellular biology.
- Molecular biology.
- 0982.
- 0379.
- 0307.
- Physical Description:
- 1 electronic resource (83 pages)
- Contained In:
- Dissertations Abstracts International 86-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2024
- Language Note:
- English
- Summary:
- Eosinophilic Esophagitis (EoE) is a chronic food allergy that causes esophageal 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 esophageal epithelial cells (EECs). However, the regulation of EEC-MHCII expression in vivo, and its contribution to esophageal food allergy, is unknown. The goal of this thesis was to determine the regulation and function of EEC-intrinsic MHCII expression in food antigen-dependent EoE. We examined the expression of MHCII-pathway transcripts in human EECs using single cell RNA-seq datasets and characterized MHCII expression patterns in biopsies from EoE patients and epithelial cell organoids. In parallel, we used a mouse model of food antigen-dependent EoE to mechanistically interrogate EEC-MHCII functions in vivo. We used gain and loss-of-function approaches to determine the contribution of IFNγ to EEC-MHCII expression in human and mouse models. Finally, we tested the effects of epithelial MHCII on EoE using ED-L2ΔI-Ab mice, which lack EEC-specific MHCII. MHCII is upregulated on EECs in active and remission EoE patients, and mice with EoE-like inflammation. In a manner similar to other non-hematopoietic cells, EEC-MHCII expression is governed by IFNγ-responsive transcriptional regulation. Interestingly, we observed that EEC-specific MHCII deficiency results in lower regulatory T cell numbers and exacerbated eosinophilic inflammation in a model of food-antigen dependent EoE. In conclusion, we herein describe the IFNγ-dependent regulation of EEC-MHCII. Importantly, we uncovered a novel immunoregulatory role for EEC-MHCII in the context of esophageal inflammation. These results expand our understanding of esophageal physiology and identify EEC-MHCII as an anti-inflammatory axis that could be leveraged to treat food allergy
- Notes:
- Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
- Advisors: Hill, David A.; Eisenlohr, Laurence C. Committee members: Silverman, Michael A.; Herbert, De'Broski R.; Ruffner, Melanie A.; Kambayashi, Taku
- Ph.D. University of Pennsylvania 2024
- Local Notes:
- School code: 0175
- ISBN:
- 9798302183910
- Access Restriction:
- Restricted for use by site license
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