{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/61246"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/61246","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"IL-27 AND THE REGULATION OF INNATE AND ADAPTIVE IMMUNITY DURING TOXOPLASMOSIS","abstract":"The cytokine IL-27 is a potent negative regulator of the inflammatory response to the pathogen Toxoplasma gondii, and the majority of the studies on IL-27 during this infection have focused on its ability to limit T cell responses. The basis for this suppressive activity is unclear, but it was proposed that the ability of IL-27 to promote T cell expression of inhibitory receptors (such as TIGIT and PD-L1) contributed to this activity. In chapter 2, the role of TIGIT during infection was assessed and indicated it was not a critical mediator of the suppressive effects of IL-27. In chapter 3, the impact of IL-27 neutralization on acute and chronic infection was examined and these data sets highlighted that in the absence of IL-27 there were enhanced monocyte responses, a cell type that does not express the IL-27R. During the later phase of infection, the overactive CD4+ T cell responses observed in the absence of IL-27 contributed to the increased monocyte response. However, analysis in chapter 4 of the most proximal events during infection-induced emergency myelopoiesis revealed that haemopoietic stem cells in the bone marrow express high levels of the IL-27R and that during infection IL-27 is a negative regulator of their differentiation into monocytes. Additionally, these studies revealed that IL-27 protected these stem cells from infection induced exhaustion. Thus, these studies highlight that IL-27 acts at multiple points during infection to limit key innate and adaptive events that contribute to infection-induced pathology.","abstract_html":"The cytokine IL-27 is a potent negative regulator of the inflammatory response to the pathogen Toxoplasma gondii, and the majority of the studies on IL-27 during this infection have focused on its ability to limit T cell responses. The basis for this suppressive activity is unclear, but it was proposed that the ability of IL-27 to promote T cell expression of inhibitory receptors (such as TIGIT and PD-L1) contributed to this activity. In chapter 2, the role of TIGIT during infection was assessed and indicated it was not a critical mediator of the suppressive effects of IL-27. In chapter 3, the impact of IL-27 neutralization on acute and chronic infection was examined and these data sets highlighted that in the absence of IL-27 there were enhanced monocyte responses, a cell type that does not express the IL-27R. During the later phase of infection, the overactive CD4+ T cell responses observed in the absence of IL-27 contributed to the increased monocyte response. However, analysis in chapter 4 of the most proximal events during infection-induced emergency myelopoiesis revealed that haemopoietic stem cells in the bone marrow express high levels of the IL-27R and that during infection IL-27 is a negative regulator of their differentiation into monocytes. Additionally, these studies revealed that IL-27 protected these stem cells from infection induced exhaustion. Thus, these studies highlight that IL-27 acts at multiple points during infection to limit key innate and adaptive events that contribute to infection-induced pathology.","abstract_has_math":false,"creators":["Aldridge, Daniel"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Hunter, Christopher"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-24T03:47:17Z","subjects":["Immunology and Infectious Disease"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/61246","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hunter, Christopher"]},{"key":"dc:creator","label":"Author","values":["Aldridge, Daniel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-11T19:10:20Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-11T19:10:20Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation/Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology and Infectious Disease"]}]},{"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://repository.upenn.edu/handle/20.500.14332/61246"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The cytokine IL-27 is a potent negative regulator of the inflammatory response to the pathogen Toxoplasma gondii, and the majority of the studies on IL-27 during this infection have focused on its ability to limit T cell responses. The basis for this suppressive activity is unclear, but it was proposed that the ability of IL-27 to promote T cell expression of inhibitory receptors (such as TIGIT and PD-L1) contributed to this activity. In chapter 2, the role of TIGIT during infection was assessed and indicated it was not a critical mediator of the suppressive effects of IL-27. In chapter 3, the impact of IL-27 neutralization on acute and chronic infection was examined and these data sets highlighted that in the absence of IL-27 there were enhanced monocyte responses, a cell type that does not express the IL-27R. During the later phase of infection, the overactive CD4+ T cell responses observed in the absence of IL-27 contributed to the increased monocyte response. However, analysis in chapter 4 of the most proximal events during infection-induced emergency myelopoiesis revealed that haemopoietic stem cells in the bone marrow express high levels of the IL-27R and that during infection IL-27 is a negative regulator of their differentiation into monocytes. Additionally, these studies revealed that IL-27 protected these stem cells from infection induced exhaustion. Thus, these studies highlight that IL-27 acts at multiple points during infection to limit key innate and adaptive events that contribute to infection-induced pathology."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:title","label":"Title","values":["IL-27 AND THE REGULATION OF INNATE AND ADAPTIVE IMMUNITY DURING TOXOPLASMOSIS"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hunter, Christopher"],"dc:creator":["Aldridge, Daniel"],"dc:date.accessioned":["2025-06-11T19:10:20Z"],"dc:date.available":["2025-06-11T19:10:20Z"],"dc:date.issued":["2025"],"dc:description.abstract":["The cytokine IL-27 is a potent negative regulator of the inflammatory response to the pathogen Toxoplasma gondii, and the majority of the studies on IL-27 during this infection have focused on its ability to limit T cell responses. The basis for this suppressive activity is unclear, but it was proposed that the ability of IL-27 to promote T cell expression of inhibitory receptors (such as TIGIT and PD-L1) contributed to this activity. In chapter 2, the role of TIGIT during infection was assessed and indicated it was not a critical mediator of the suppressive effects of IL-27. In chapter 3, the impact of IL-27 neutralization on acute and chronic infection was examined and these data sets highlighted that in the absence of IL-27 there were enhanced monocyte responses, a cell type that does not express the IL-27R. During the later phase of infection, the overactive CD4+ T cell responses observed in the absence of IL-27 contributed to the increased monocyte response. However, analysis in chapter 4 of the most proximal events during infection-induced emergency myelopoiesis revealed that haemopoietic stem cells in the bone marrow express high levels of the IL-27R and that during infection IL-27 is a negative regulator of their differentiation into monocytes. Additionally, these studies revealed that IL-27 protected these stem cells from infection induced exhaustion. Thus, these studies highlight that IL-27 acts at multiple points during infection to limit key innate and adaptive events that contribute to infection-induced pathology."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/61246"],"dc:language.iso":["en"],"dc:subject":["Immunology and Infectious Disease"],"dc:title":["IL-27 AND THE REGULATION OF INNATE AND ADAPTIVE IMMUNITY DURING TOXOPLASMOSIS"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:47:17Z"}