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dc.contributor.advisorKatherine A. Fitzgeralden_US
dc.contributor.authorLei, Xuqiu
dc.date.accessioned2022-10-31T22:39:22Z
dc.date.available2022-10-31T22:39:22Z
dc.date.issued2022-10-19
dc.identifier.doi10.13028/r81y-tc35en_US
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51245
dc.description.abstractHepatocyte nuclear factor 4 alpha (HNF4A) is a highly conserved nuclear receptor that has been associated with ulcerative colitis. In mice, HNF4A is indispensable for the maintenance of intestinal homeostasis, yet the underlying mechanisms are poorly characterized. Here we demonstrate that the expression of HNF4A in intestinal epithelial cells (IECs) is required for the proper development and composition of the intraepithelial lymphocyte (IEL) compartment. HNF4A directly regulates expression of immune signaling molecules including butyrophilin-like (Btnl) 1, Btnl6, H2-T3, and Clec2e that control IEC-IEL crosstalk. HNF4A selectively enhances the expansion of natural IELs that are TCRγδ+ or TCRαβ+CD8αα+ to shape the composition of IEL compartment. In the small intestine, HNF4A cooperates with its paralog HNF4G, to drive expression of immune signaling molecules. Moreover, the HNF4A-BTNL regulatory axis is conserved in human IECs. Collectively, these findings underscore the importance of HNF4A as a conserved transcription factor controlling IEC-IEL crosstalk and suggest that HNF4A maintains intestinal homeostasis through regulation of the IEL compartment.en_US
dc.language.isoen_USen_US
dc.publisherUMass Chan Medical Schoolen_US
dc.relation<p>Part of the work was published in J Exp Med. <a href="https://doi.org/10.1084/jem.20212563" target="_blank" title="Published work in Journal of Experimental Medicine">https://doi.org/10.1084/jem.20212563</a>.</p> <p>RNA-seq datasets are available on NCBI Gene Expression Omnibus <a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE199417" target="_blank" title="GSE199417">(accession number GSE199417)</a>.</p>en_US
dc.rightsCopyright © 2022 Xuqiu Lei.en_US
dc.rights.uriAll Rights Reserveden_US
dc.subjectHNF4Aen_US
dc.subjectinflammatory bowel diseaseen_US
dc.subjectintestinal homeostasisen_US
dc.subjectintestinal inflammationen_US
dc.subjectintraepithelial lymphocytesen_US
dc.subjectγδ Ten_US
dc.subjectbutyrophilinen_US
dc.subjectHNF4Gen_US
dc.titleInvestigating HNF4A in Intestinal Homeostasis and Inflammationen_US
dc.typeDoctoral Dissertationen_US
atmire.contributor.authoremailxuqiu.lei@umassmed.eduen_US
dc.contributor.departmentMedicineen_US
dc.description.thesisprogramImmunology and Microbiologyen_US
dc.identifier.orcid0000-0003-3565-6969en_US


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