000009716 001__ 9716 000009716 005__ 20231129124950.0 000009716 0247_ $$2DOI$$a10.6083/v979v391t 000009716 037__ $$aETD 000009716 245__ $$aCharacterizing the dominant role of interferon-lambda (IFN-λ) signaling in the intestinal epithelium 000009716 260__ $$bOregon Health and Science University 000009716 269__ $$a2022 000009716 336__ $$aDissertation 000009716 502__ $$bPh.D. 000009716 520__ $$aInterferon (IFN) family cytokines stimulate a broad group of genes known as interferon stimulated gene (ISGs). The primary function of ISGs is to provide antiviral host defense. IFN-α and IFN-β signal through IFN-α receptor (IFNAR) whereas IFN-λ signals through IFN-λ receptor (IFNLR). IFNAR is expressed by many cell types, but IFNLR is primarily expressed by epithelial cells in barrier tissues. However, unlike most epithelial barriers that respond to both IFN-λ and IFN-α/β, intestinal epithelial cells (IECs) preferentially respond to IFN-λ and are hyporesponsive to IFN-α/β. As such, IFN-λ has a dominant role in protecting IECs from enteric viruses. The physiological rationale for this selective responsiveness by IECs is poorly understood. Furthermore, the interactions of IFN-λ signaling in IECs with the environmental context of bacterial microbiota have not been determined. In this dissertation, I describe the consequences and contexts surrounding the IFN-λ response by IECs. 000009716 542__ $$fIn copyright - single owner 000009716 650__ $$aIntestinal Mucosa$$020954 000009716 650__ $$aEpithelial Cells$$018550 000009716 650__ $$aInterferons$$020914 000009716 650__ $$aRotavirus$$025610 000009716 650__ $$aGastrointestinal Microbiome$$011348 000009716 650__ $$aOrganoids$$023278 000009716 650__ $$aTumor Necrosis Factor-alpha$$027502 000009716 691__ $$aSchool of Medicine$$041369 000009716 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429 000009716 7001_ $$aVan Winkle, Jacob A. 000009716 8564_ $$962b04766-c4e8-49fe-b05d-273b0f7630b9$$s8032697$$uhttps://digitalcollections.ohsu.edu/record/9716/files/VanWinkle.Jacob.2022.pdf 000009716 905__ $$a/rest/prod/v9/79/v3/91/v979v391t 000009716 909CO $$ooai:digitalcollections.ohsu.edu:9716$$pstudent-work 000009716 980__ $$aTheses and Dissertations