{"id":{"repo_id":"tdl","oai_identifier":"oai:tdl-ir.tdl.org:20.500.12588/7328"},"canonical_url":"https://search.dev.ndltd.org/etd/tdl/oai:tdl-ir.tdl.org:20.500.12588/7328","repository":{"repo_id":"tdl","name":"Texas Digital Library","base_url":"https://tdl-ir.tdl.org/server/oai/request"},"display":{"title":"IFN-γ Induced Nitric Oxide Leads to the Inhibition of TH17 Differentiation via iNOS","abstract":"Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), driven by autoreactive T cells that mediate demyelination, axonal loss, and neuroinflammation. Among the pathogenic T helper subsets, Th17 cells are pivotal in MS progression, producing high levels of proinflammatory cytokines such as IL-17. While Interferon-gamma (IFN-γ) is traditionally seen as proinflammatory, recent findings highlight a paradoxical protective role by inhibiting Th17 differentiation. In this thesis, we explored how IFN-γ, through its regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, influences Th1 and Th17 responses in the Experimental Autoimmune Encephalomyelitis (EAE) model and in vitro T cell assays. Our results demonstrate that the absence of IFN-γ signaling exacerbates EAE severity and elevates Th17 cell frequency, underscoring IFN-γ’s protective capacity. In vitro, IFN-γ dose-dependently suppresses Th17 differentiation while promoting Th1 responses. Contrary to expectations, iNOS inhibition did not significantly enhance Th17 cells, though the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) boosted Th1 cells and modestly reduced Th17 cells. Notably, IFN-γ signaling was necessary for robust iNOS expression during EAE, pointing to a critical IFN-γ–iNOS–NO axis in regulating Th17-driven pathology. These findings underscore the complex role of IFN-γ in modulating Th17 responses and highlight potential therapeutic targets involving NO pathways to mitigate autoimmune inflammation in MS.","abstract_html":"Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), driven by autoreactive T cells that mediate demyelination, axonal loss, and neuroinflammation. Among the pathogenic T helper subsets, Th17 cells are pivotal in MS progression, producing high levels of proinflammatory cytokines such as IL-17. While Interferon-gamma (IFN-γ) is traditionally seen as proinflammatory, recent findings highlight a paradoxical protective role by inhibiting Th17 differentiation. In this thesis, we explored how IFN-γ, through its regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, influences Th1 and Th17 responses in the Experimental Autoimmune Encephalomyelitis (EAE) model and in vitro T cell assays. Our results demonstrate that the absence of IFN-γ signaling exacerbates EAE severity and elevates Th17 cell frequency, underscoring IFN-γ’s protective capacity. In vitro, IFN-γ dose-dependently suppresses Th17 differentiation while promoting Th1 responses. Contrary to expectations, iNOS inhibition did not significantly enhance Th17 cells, though the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) boosted Th1 cells and modestly reduced Th17 cells. Notably, IFN-γ signaling was necessary for robust iNOS expression during EAE, pointing to a critical IFN-γ–iNOS–NO axis in regulating Th17-driven pathology. These findings underscore the complex role of IFN-γ in modulating Th17 responses and highlight potential therapeutic targets involving NO pathways to mitigate autoimmune inflammation in MS.","abstract_has_math":false,"creators":["Naseem, Yashfa"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Forsthuber, Thomas","Ramos, William","Guentzel, Neal"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-27T21:19:13Z","subjects":["EAE","IFN-γ","iNOS","Nitric Oxide (NO)","TH17","Central nervous system","Multiple Sclerosis","Autoimmune disease","T cell assays"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9798314895948"],"render_values":[{"text":"9798314895948","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/20.500.12588/7328","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Forsthuber, Thomas","Ramos, William","Guentzel, Neal"]},{"key":"dc:creator","label":"Author","values":["Naseem, Yashfa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-03-25T16:22:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["EAE","IFN-γ","iNOS","Nitric Oxide (NO)","TH17","Central nervous system","Multiple Sclerosis","Autoimmune disease","T cell assays"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9798314895948","https://hdl.handle.net/20.500.12588/7328"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.12588/7328"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), driven by autoreactive T cells that mediate demyelination, axonal loss, and neuroinflammation. Among the pathogenic T helper subsets, Th17 cells are pivotal in MS progression, producing high levels of proinflammatory cytokines such as IL-17. While Interferon-gamma (IFN-γ) is traditionally seen as proinflammatory, recent findings highlight a paradoxical protective role by inhibiting Th17 differentiation. In this thesis, we explored how IFN-γ, through its regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, influences Th1 and Th17 responses in the Experimental Autoimmune Encephalomyelitis (EAE) model and in vitro T cell assays. Our results demonstrate that the absence of IFN-γ signaling exacerbates EAE severity and elevates Th17 cell frequency, underscoring IFN-γ’s protective capacity. In vitro, IFN-γ dose-dependently suppresses Th17 differentiation while promoting Th1 responses. Contrary to expectations, iNOS inhibition did not significantly enhance Th17 cells, though the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) boosted Th1 cells and modestly reduced Th17 cells. Notably, IFN-γ signaling was necessary for robust iNOS expression during EAE, pointing to a critical IFN-γ–iNOS–NO axis in regulating Th17-driven pathology. These findings underscore the complex role of IFN-γ in modulating Th17 responses and highlight potential therapeutic targets involving NO pathways to mitigate autoimmune inflammation in MS."]},{"key":"dc:title","label":"Title","values":["IFN-γ Induced Nitric Oxide Leads to the Inhibition of TH17 Differentiation via iNOS"]}]}],"canonical_facts":{"dc:contributor":["Forsthuber, Thomas","Ramos, William","Guentzel, Neal"],"dc:creator":["Naseem, Yashfa"],"dc:date.accessioned":["2026-03-25T16:22:05Z"],"dc:date.issued":["2025"],"dc:description.abstract":["Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), driven by autoreactive T cells that mediate demyelination, axonal loss, and neuroinflammation. Among the pathogenic T helper subsets, Th17 cells are pivotal in MS progression, producing high levels of proinflammatory cytokines such as IL-17. While Interferon-gamma (IFN-γ) is traditionally seen as proinflammatory, recent findings highlight a paradoxical protective role by inhibiting Th17 differentiation. In this thesis, we explored how IFN-γ, through its regulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, influences Th1 and Th17 responses in the Experimental Autoimmune Encephalomyelitis (EAE) model and in vitro T cell assays. Our results demonstrate that the absence of IFN-γ signaling exacerbates EAE severity and elevates Th17 cell frequency, underscoring IFN-γ’s protective capacity. In vitro, IFN-γ dose-dependently suppresses Th17 differentiation while promoting Th1 responses. Contrary to expectations, iNOS inhibition did not significantly enhance Th17 cells, though the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) boosted Th1 cells and modestly reduced Th17 cells. Notably, IFN-γ signaling was necessary for robust iNOS expression during EAE, pointing to a critical IFN-γ–iNOS–NO axis in regulating Th17-driven pathology. These findings underscore the complex role of IFN-γ in modulating Th17 responses and highlight potential therapeutic targets involving NO pathways to mitigate autoimmune inflammation in MS."],"dc:identifier":["9798314895948","https://hdl.handle.net/20.500.12588/7328"],"dc:identifier.uri":["https://hdl.handle.net/20.500.12588/7328"],"dc:language":["eng"],"dc:subject":["EAE","IFN-γ","iNOS","Nitric Oxide (NO)","TH17","Central nervous system","Multiple Sclerosis","Autoimmune disease","T cell assays"],"dc:title":["IFN-γ Induced Nitric Oxide Leads to the Inhibition of TH17 Differentiation via iNOS"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:19:13Z"}