{"id":{"repo_id":"iupui","oai_identifier":"oai:scholarworks.indianapolis.iu.edu:1805/55152"},"canonical_url":"https://search.dev.ndltd.org/etd/iupui/oai:scholarworks.indianapolis.iu.edu:1805/55152","repository":{"repo_id":"iupui","name":"IUPUI","base_url":"https://scholarworks.indianapolis.iu.edu/server/oai/request"},"display":{"title":"The Impact of IL-9 on Disease in Murine Models of Systemic Lupus Erythematosus","abstract":"Systemic lupus erythematosus (SLE) is a relapsing-remitting antibody-mediated autoimmune disease characterized by systemic immune complex deposition. A subset of SLE patients has been shown to have elevated CD4+IL-9+ T cells as well as increased secreted IL-9 and Il9 mRNA compared to healthy controls. In other antibody mediated autoimmune models, such as rheumatoid arthritis, type II innate lymphoid cells (ILC2s) secrete increased IL-9 to promote the suppressive response of regulatory T (Treg) cells. As such, the role of IL-9 may be context-dependent and requires further investigation in SLE. This thesis examines standard and novel murine models of SLE to demonstrate that IL-9 exhibits both protective and proinflammatory functions, consistent with IL-9 activity varying with disease progression. Within our model, the use of an IL-9 neutralizing antibody (Ab) for 6 weeks in 6-week-old mice results in an exacerbation of disease and an expansion of immune cell subsets that promote autoimmunity. Anti-IL-9 Ab treatment also results in a loss of Treg cells and IL-9+ ILC2s in the kidney, which suggests that IL-9 promotes a protective response. From 6 to 12 weeks of treatment, the anti-IL-9 Ab treatment does not result in significant disease exacerbation compared to the isotype control. In parallel, we used a chimeric antigen receptor (CAR)-T cell approach, which is a promising treatment option for SLE patients, to test whether a third generation CAR-T cell can be polarized to a CAR-T9 cell and mitigate SLE disease severity. Our preliminary results indicate a reduction in CD19+ B cells and lymphoproliferation in the CAR-T9 cell treated SLE mice. Ultimately, our data suggests that IL-9 has a protective effect at early time points of disease, and this finding could be harnessed for cellular therapies of disease.","abstract_html":"Systemic lupus erythematosus (SLE) is a relapsing-remitting antibody-mediated autoimmune disease characterized by systemic immune complex deposition. A subset of SLE patients has been shown to have elevated CD4+IL-9+ T cells as well as increased secreted IL-9 and Il9 mRNA compared to healthy controls. In other antibody mediated autoimmune models, such as rheumatoid arthritis, type II innate lymphoid cells (ILC2s) secrete increased IL-9 to promote the suppressive response of regulatory T (Treg) cells. As such, the role of IL-9 may be context-dependent and requires further investigation in SLE. This thesis examines standard and novel murine models of SLE to demonstrate that IL-9 exhibits both protective and proinflammatory functions, consistent with IL-9 activity varying with disease progression. Within our model, the use of an IL-9 neutralizing antibody (Ab) for 6 weeks in 6-week-old mice results in an exacerbation of disease and an expansion of immune cell subsets that promote autoimmunity. Anti-IL-9 Ab treatment also results in a loss of Treg cells and IL-9+ ILC2s in the kidney, which suggests that IL-9 promotes a protective response. From 6 to 12 weeks of treatment, the anti-IL-9 Ab treatment does not result in significant disease exacerbation compared to the isotype control. In parallel, we used a chimeric antigen receptor (CAR)-T cell approach, which is a promising treatment option for SLE patients, to test whether a third generation CAR-T cell can be polarized to a CAR-T9 cell and mitigate SLE disease severity. Our preliminary results indicate a reduction in CD19+ B cells and lymphoproliferation in the CAR-T9 cell treated SLE mice. Ultimately, our data suggests that IL-9 has a protective effect at early time points of disease, and this finding could be harnessed for cellular therapies of disease.","abstract_has_math":false,"creators":["Krishnan, Maya Shraddha"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Kaplan, Mark H."],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-03","date_published":"2026-03","updated_at":"2026-07-24T02:41:52Z","subjects":["antibody","cytokines","immunotherapy","lupus"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1805/55152","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kaplan, Mark H."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Rhodes, Steven","Richer, Martin","Snell, Laura","Zhou, Baohua"]},{"key":"dc:creator","label":"Author","values":["Krishnan, Maya Shraddha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-04-08T13:00:11Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2026-04-08T13:00:11Z"]},{"key":"dc:date.issued","label":"Date","values":["2026-03"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["antibody","cytokines","immunotherapy","lupus"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1805/55152"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["IUI"]},{"key":"dc:description.abstract","label":"Abstract","values":["Systemic lupus erythematosus (SLE) is a relapsing-remitting antibody-mediated autoimmune disease characterized by systemic immune complex deposition. A subset of SLE patients has been shown to have elevated CD4+IL-9+ T cells as well as increased secreted IL-9 and Il9 mRNA compared to healthy controls. In other antibody mediated autoimmune models, such as rheumatoid arthritis, type II innate lymphoid cells (ILC2s) secrete increased IL-9 to promote the suppressive response of regulatory T (Treg) cells. As such, the role of IL-9 may be context-dependent and requires further investigation in SLE. This thesis examines standard and novel murine models of SLE to demonstrate that IL-9 exhibits both protective and proinflammatory functions, consistent with IL-9 activity varying with disease progression. Within our model, the use of an IL-9 neutralizing antibody (Ab) for 6 weeks in 6-week-old mice results in an exacerbation of disease and an expansion of immune cell subsets that promote autoimmunity. Anti-IL-9 Ab treatment also results in a loss of Treg cells and IL-9+ ILC2s in the kidney, which suggests that IL-9 promotes a protective response. From 6 to 12 weeks of treatment, the anti-IL-9 Ab treatment does not result in significant disease exacerbation compared to the isotype control. In parallel, we used a chimeric antigen receptor (CAR)-T cell approach, which is a promising treatment option for SLE patients, to test whether a third generation CAR-T cell can be polarized to a CAR-T9 cell and mitigate SLE disease severity. Our preliminary results indicate a reduction in CD19+ B cells and lymphoproliferation in the CAR-T9 cell treated SLE mice. Ultimately, our data suggests that IL-9 has a protective effect at early time points of disease, and this finding could be harnessed for cellular therapies of disease."]},{"key":"dc:title","label":"Title","values":["The Impact of IL-9 on Disease in Murine Models of Systemic Lupus Erythematosus"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kaplan, Mark H."],"dc:contributor.other":["Rhodes, Steven","Richer, Martin","Snell, Laura","Zhou, Baohua"],"dc:creator":["Krishnan, Maya Shraddha"],"dc:date.accessioned":["2026-04-08T13:00:11Z"],"dc:date.available":["2026-04-08T13:00:11Z"],"dc:date.issued":["2026-03"],"dc:description":["IUI"],"dc:description.abstract":["Systemic lupus erythematosus (SLE) is a relapsing-remitting antibody-mediated autoimmune disease characterized by systemic immune complex deposition. A subset of SLE patients has been shown to have elevated CD4+IL-9+ T cells as well as increased secreted IL-9 and Il9 mRNA compared to healthy controls. In other antibody mediated autoimmune models, such as rheumatoid arthritis, type II innate lymphoid cells (ILC2s) secrete increased IL-9 to promote the suppressive response of regulatory T (Treg) cells. As such, the role of IL-9 may be context-dependent and requires further investigation in SLE. This thesis examines standard and novel murine models of SLE to demonstrate that IL-9 exhibits both protective and proinflammatory functions, consistent with IL-9 activity varying with disease progression. Within our model, the use of an IL-9 neutralizing antibody (Ab) for 6 weeks in 6-week-old mice results in an exacerbation of disease and an expansion of immune cell subsets that promote autoimmunity. Anti-IL-9 Ab treatment also results in a loss of Treg cells and IL-9+ ILC2s in the kidney, which suggests that IL-9 promotes a protective response. From 6 to 12 weeks of treatment, the anti-IL-9 Ab treatment does not result in significant disease exacerbation compared to the isotype control. In parallel, we used a chimeric antigen receptor (CAR)-T cell approach, which is a promising treatment option for SLE patients, to test whether a third generation CAR-T cell can be polarized to a CAR-T9 cell and mitigate SLE disease severity. Our preliminary results indicate a reduction in CD19+ B cells and lymphoproliferation in the CAR-T9 cell treated SLE mice. Ultimately, our data suggests that IL-9 has a protective effect at early time points of disease, and this finding could be harnessed for cellular therapies of disease."],"dc:identifier.uri":["https://hdl.handle.net/1805/55152"],"dc:language.iso":["en_US"],"dc:subject":["antibody","cytokines","immunotherapy","lupus"],"dc:title":["The Impact of IL-9 on Disease in Murine Models of Systemic Lupus Erythematosus"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T02:41:52Z"}