{"id":{"repo_id":"umn","oai_identifier":"oai:conservancy.umn.edu:11299/264329"},"canonical_url":"https://search.dev.ndltd.org/etd/umn/oai:conservancy.umn.edu:11299/264329","repository":{"repo_id":"umn","name":"University of Minnesota","base_url":"https://conservancy.umn.edu/server/oai/request"},"display":{"title":"Characterizing the role of thymic interferon in T cell development and selection","abstract":"Type I and III interferons (IFNs) are robustly induced during infections, where they protect cells against viral infection and activate immune cells. Curiously, both type I and type III IFNs were reported to be produced at low levels in the thymus in the absence of infection – the site of T cell development and a crucial organ for immune tolerance.To understand the impact of IFNs on T cell development and immune tolerance, we identified the cells that produce and respond to IFN. We found that both type I and III IFNs were constitutively produced by a very small number of AIRE+ thymic epithelial cells, independent of microbial stimulation. Antigen presenting cells were highly responsive to thymic IFNs and IFNs were required for the activation and maturation of thymic DC1, macrophages and B cells. Loss of IFN-sensing led to reduced T regulatory cell selection, reduced T cell receptor (TCR) repertoire diversity and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to interferons in the thymus is required for generating a safe and diverse TCR repertoire. Furthermore, recent reports have identified strongly IFN-signaled populations of mature naïve T cells in the periphery, suggestive of unappreciated heterogeneity within the naïve T cell pool. In light of these findings, we were curious to determine whether type I IFN signaling in the thymus impacted T cell fate. To this end, we used Mx1-lineage tracing mice, in which Cre- expression is controlled by the IFN-responsive Mx1 promoter, to track IFN experienced T cells.","abstract_html":"Type I and III interferons (IFNs) are robustly induced during infections, where they protect cells against viral infection and activate immune cells. Curiously, both type I and type III IFNs were reported to be produced at low levels in the thymus in the absence of infection – the site of T cell development and a crucial organ for immune tolerance.To understand the impact of IFNs on T cell development and immune tolerance, we identified the cells that produce and respond to IFN. We found that both type I and III IFNs were constitutively produced by a very small number of AIRE+ thymic epithelial cells, independent of microbial stimulation. Antigen presenting cells were highly responsive to thymic IFNs and IFNs were required for the activation and maturation of thymic DC1, macrophages and B cells. Loss of IFN-sensing led to reduced T regulatory cell selection, reduced T cell receptor (TCR) repertoire diversity and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to interferons in the thymus is required for generating a safe and diverse TCR repertoire. Furthermore, recent reports have identified strongly IFN-signaled populations of mature naïve T cells in the periphery, suggestive of unappreciated heterogeneity within the naïve T cell pool. In light of these findings, we were curious to determine whether type I IFN signaling in the thymus impacted T cell fate. To this end, we used Mx1-lineage tracing mice, in which Cre- expression is controlled by the IFN-responsive Mx1 promoter, to track IFN experienced T cells.","abstract_has_math":false,"creators":["Ashby, Katherine"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-04","date_published":"2024-04","updated_at":"2026-07-24T05:19:54Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/11299/264329","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Ashby, Katherine"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-07-24T21:52:27Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-07-24T21:52:27Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-04"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/11299/264329"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["University of Minnesota Ph.D. dissertation.April 2024. Major: Microbiology, Immunology and Cancer Biology. Advisor: Kristin Hogquist. 1 computer file (PDF); vii, 109 pages."]},{"key":"dc:description.abstract","label":"Abstract","values":["Type I and III interferons (IFNs) are robustly induced during infections, where they protect cells against viral infection and activate immune cells. Curiously, both type I and type III IFNs were reported to be produced at low levels in the thymus in the absence of infection – the site of T cell development and a crucial organ for immune tolerance.To understand the impact of IFNs on T cell development and immune tolerance, we identified the cells that produce and respond to IFN. We found that both type I and III IFNs were constitutively produced by a very small number of AIRE+ thymic epithelial cells, independent of microbial stimulation. Antigen presenting cells were highly responsive to thymic IFNs and IFNs were required for the activation and maturation of thymic DC1, macrophages and B cells. Loss of IFN-sensing led to reduced T regulatory cell selection, reduced T cell receptor (TCR) repertoire diversity and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to interferons in the thymus is required for generating a safe and diverse TCR repertoire. Furthermore, recent reports have identified strongly IFN-signaled populations of mature naïve T cells in the periphery, suggestive of unappreciated heterogeneity within the naïve T cell pool. In light of these findings, we were curious to determine whether type I IFN signaling in the thymus impacted T cell fate. To this end, we used Mx1-lineage tracing mice, in which Cre- expression is controlled by the IFN-responsive Mx1 promoter, to track IFN experienced T cells."]},{"key":"dc:title","label":"Title","values":["Characterizing the role of thymic interferon in T cell development and selection"]}]}],"canonical_facts":{"dc:creator":["Ashby, Katherine"],"dc:date.accessioned":["2024-07-24T21:52:27Z"],"dc:date.available":["2024-07-24T21:52:27Z"],"dc:date.issued":["2024-04"],"dc:description":["University of Minnesota Ph.D. dissertation.April 2024. Major: Microbiology, Immunology and Cancer Biology. Advisor: Kristin Hogquist. 1 computer file (PDF); vii, 109 pages."],"dc:description.abstract":["Type I and III interferons (IFNs) are robustly induced during infections, where they protect cells against viral infection and activate immune cells. Curiously, both type I and type III IFNs were reported to be produced at low levels in the thymus in the absence of infection – the site of T cell development and a crucial organ for immune tolerance.To understand the impact of IFNs on T cell development and immune tolerance, we identified the cells that produce and respond to IFN. We found that both type I and III IFNs were constitutively produced by a very small number of AIRE+ thymic epithelial cells, independent of microbial stimulation. Antigen presenting cells were highly responsive to thymic IFNs and IFNs were required for the activation and maturation of thymic DC1, macrophages and B cells. Loss of IFN-sensing led to reduced T regulatory cell selection, reduced T cell receptor (TCR) repertoire diversity and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to interferons in the thymus is required for generating a safe and diverse TCR repertoire. Furthermore, recent reports have identified strongly IFN-signaled populations of mature naïve T cells in the periphery, suggestive of unappreciated heterogeneity within the naïve T cell pool. In light of these findings, we were curious to determine whether type I IFN signaling in the thymus impacted T cell fate. To this end, we used Mx1-lineage tracing mice, in which Cre- expression is controlled by the IFN-responsive Mx1 promoter, to track IFN experienced T cells."],"dc:identifier.uri":["https://hdl.handle.net/11299/264329"],"dc:language.iso":["en"],"dc:title":["Characterizing the role of thymic interferon in T cell development and selection"],"dc:type":["Thesis or Dissertation"]},"updated_at":"2026-07-24T05:19:54Z"}