{"id":{"repo_id":"calgary","oai_identifier":"oai:ucalgary.scholaris.ca:1880/121010"},"canonical_url":"https://search.dev.ndltd.org/etd/calgary/oai:ucalgary.scholaris.ca:1880/121010","repository":{"repo_id":"calgary","name":"University of Calgary","base_url":"https://ucalgary.scholaris.ca/server/oai/request"},"display":{"title":"Inflammatory astrocyte and T cell interactions are supported by hyaluronan in a murine model of Multiple Sclerosis","abstract":"Multiple Sclerosis (MS) is an autoimmune disorder characterized by demyelination, neurodegeneration, and immune cell infiltration into the central nervous system (CNS). Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are thought to play a role in the development of demyelinating lesions. In this thesis, I characterized the distribution of inflammatory astrocytes and their interactions in the experimental autoimmune encephalomyelitis (EAE) model of MS. Using this model and in vitro cultures of astrocytes, I identified a novel cell surface marker to identify inflammatory astrocytes. By flow cytometry and confocal microscopy, I determined that the frequency of inflammatory astrocytes is significantly increased in the acute and chronic stages of EAE. I determined that CD4+ T cells are spatially closer to inflammatory astrocytes in EAE tissue, compared to control tissue, and maintain this close distance throughout disease. I further observed that inflammatory astrocytes extend their processes and physically envelop T cells in EAE. In addition, when inflammatory astrocytes and activated T cells are cultured together, the viability of T cells is increased. Moreover, I found that in vitro generated inflammatory astrocytes have increased expression of hyaluronan synthases. Hyaluronan is an extracellular matrix component that is primarily released by astrocytes in the CNS. It has been shown to accumulate in MS and EAE lesions and is thought to support encephalitogenic properties of T cells. However, if astrocyte were treated with the drug 4-methylumbelliferone, which reduces hyaluronan synthesis, this effect on T cell viability is abrogated. Together, my findings suggest that inflammatory astrocytes play a pathogenic role in the progression of EAE through their interactions with T cells, which may be supported by their release of hyaluronan.","abstract_html":"Multiple Sclerosis (MS) is an autoimmune disorder characterized by demyelination, neurodegeneration, and immune cell infiltration into the central nervous system (CNS). Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are thought to play a role in the development of demyelinating lesions. In this thesis, I characterized the distribution of inflammatory astrocytes and their interactions in the experimental autoimmune encephalomyelitis (EAE) model of MS. Using this model and in vitro cultures of astrocytes, I identified a novel cell surface marker to identify inflammatory astrocytes. By flow cytometry and confocal microscopy, I determined that the frequency of inflammatory astrocytes is significantly increased in the acute and chronic stages of EAE. I determined that CD4+ T cells are spatially closer to inflammatory astrocytes in EAE tissue, compared to control tissue, and maintain this close distance throughout disease. I further observed that inflammatory astrocytes extend their processes and physically envelop T cells in EAE. In addition, when inflammatory astrocytes and activated T cells are cultured together, the viability of T cells is increased. Moreover, I found that in vitro generated inflammatory astrocytes have increased expression of hyaluronan synthases. Hyaluronan is an extracellular matrix component that is primarily released by astrocytes in the CNS. It has been shown to accumulate in MS and EAE lesions and is thought to support encephalitogenic properties of T cells. However, if astrocyte were treated with the drug 4-methylumbelliferone, which reduces hyaluronan synthesis, this effect on T cell viability is abrogated. Together, my findings suggest that inflammatory astrocytes play a pathogenic role in the progression of EAE through their interactions with T cells, which may be supported by their release of hyaluronan.","abstract_has_math":false,"creators":["Reid, Jacqueline Kelsey"],"institution":"Graduate Studies","degree_name":"Doctor of Philosophy (PhD)","degree_level":null,"degree_discipline":"Medicine – Neuroscience","degree_department":null,"school":null,"contributors":[],"advisors":["Kuipers, Hedwich","Yong, Wee V."],"committee_chairs":[],"committee_members":["Gordon, Grant","Jirik, Frank"],"year":2025,"date_issued":"2025-03-26","date_published":"2025-03-26","updated_at":"2026-07-24T01:30:13Z","subjects":[],"languages":["en"],"rights":["University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://dx.doi.org/10.11575/PRISM/48600"],"render_values":[{"text":"https://dx.doi.org/10.11575/PRISM/48600","href":"https://dx.doi.org/10.11575/PRISM/48600","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1880/121010","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kuipers, Hedwich","Yong, Wee V."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Gordon, Grant","Jirik, Frank"]},{"key":"dc:creator","label":"Author","values":["Reid, Jacqueline Kelsey"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-06"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-04-16T15:11:04Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-04-16T15:11:04Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-03-26"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Calgary"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medicine – Neuroscience"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Calgary"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["University of Calgary graduate students retain copyright ownership and moral rights for their thesis. 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In this thesis, I characterized the distribution of inflammatory astrocytes and their interactions in the experimental autoimmune encephalomyelitis (EAE) model of MS. Using this model and in vitro cultures of astrocytes, I identified a novel cell surface marker to identify inflammatory astrocytes. By flow cytometry and confocal microscopy, I determined that the frequency of inflammatory astrocytes is significantly increased in the acute and chronic stages of EAE. I determined that CD4+ T cells are spatially closer to inflammatory astrocytes in EAE tissue, compared to control tissue, and maintain this close distance throughout disease. I further observed that inflammatory astrocytes extend their processes and physically envelop T cells in EAE. In addition, when inflammatory astrocytes and activated T cells are cultured together, the viability of T cells is increased. Moreover, I found that in vitro generated inflammatory astrocytes have increased expression of hyaluronan synthases. Hyaluronan is an extracellular matrix component that is primarily released by astrocytes in the CNS. It has been shown to accumulate in MS and EAE lesions and is thought to support encephalitogenic properties of T cells. However, if astrocyte were treated with the drug 4-methylumbelliferone, which reduces hyaluronan synthesis, this effect on T cell viability is abrogated. Together, my findings suggest that inflammatory astrocytes play a pathogenic role in the progression of EAE through their interactions with T cells, which may be supported by their release of hyaluronan."]},{"key":"dc:title","label":"Title","values":["Inflammatory astrocyte and T cell interactions are supported by hyaluronan in a murine model of Multiple Sclerosis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kuipers, Hedwich","Yong, Wee V."],"dc:contributor.committeemember":["Gordon, Grant","Jirik, Frank"],"dc:creator":["Reid, Jacqueline Kelsey"],"dc:date":["2025-06"],"dc:date.accessioned":["2025-04-16T15:11:04Z"],"dc:date.available":["2025-04-16T15:11:04Z"],"dc:date.issued":["2025-03-26"],"dc:description.abstract":["Multiple Sclerosis (MS) is an autoimmune disorder characterized by demyelination, neurodegeneration, and immune cell infiltration into the central nervous system (CNS). 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In addition, when inflammatory astrocytes and activated T cells are cultured together, the viability of T cells is increased. Moreover, I found that in vitro generated inflammatory astrocytes have increased expression of hyaluronan synthases. Hyaluronan is an extracellular matrix component that is primarily released by astrocytes in the CNS. It has been shown to accumulate in MS and EAE lesions and is thought to support encephalitogenic properties of T cells. However, if astrocyte were treated with the drug 4-methylumbelliferone, which reduces hyaluronan synthesis, this effect on T cell viability is abrogated. Together, my findings suggest that inflammatory astrocytes play a pathogenic role in the progression of EAE through their interactions with T cells, which may be supported by their release of hyaluronan."],"dc:identifier.doi":["https://dx.doi.org/10.11575/PRISM/48600"],"dc:identifier.uri":["https://hdl.handle.net/1880/121010"],"dc:language.iso":["en"],"dc:publisher.institution":["University of Calgary"],"dc:rights":["University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission."],"dc:title":["Inflammatory astrocyte and T cell interactions are supported by hyaluronan in a murine model of Multiple Sclerosis"],"dc:type":["doctoral thesis"],"thesis:degree_discipline":["Medicine – Neuroscience"],"thesis:degree_name":["Doctor of Philosophy (PhD)"],"thesis:institution_name":["University of Calgary"]},"updated_at":"2026-07-24T01:30:13Z"}