{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/14872"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/14872","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"The Role of Apolipoprotein A-I in the Modulation of Cholesterol and Immune Homeostasis","abstract":"The goal of this work was to examine the role of apoA-I in atherosclerosis and autoimmunity. We used a mouse model lacking the LDL receptor and the apoA-I gene (LDLr-/-,ApoA-I-/- or DKO). LDLr-/- (SKO) mice were used as controls. When fed a cholesterol-containing diet, DKO mice exhibited cholesterol accumulation in the skin and skin-draining lymph nodes (LNs). The LN total cell number was increased, with expansion of T cell, B cell, dendritic cell (DC) and macrophage populations. Interestingly, DKO LN T cells, B cells and DCs had increased cholesterol compared to controls. DKO LN T cells had increased expression of activation markers and proliferation of CD4+CD44high T cells was increased. Plasma autoantibodies were also increased. We concluded that, in the absence of apoA-I, diet-fed DKO mice develop an autoimmune phenotype. These data suggest that apoA-I can modulate immune cell function by regulating cellular cholesterol balance. This, in turn, prevents LN cell expansion, activation and the progression of atherosclerosis. Regulatory T cells (Treg) were increased in LNs of DKO mice. To determine the direct effects of apoA-I on this cell population and the autoimmune phenotype, mice were fed diet for 6 weeks then apoA-I injections began and continued every 48 hours for an additional 6 weeks. After 12 weeks total on diet, apoA-I-treated DKO mice (DKO+A-I) had reduced LN size and reduced LN cell number compared to DKO mice treated with BSA (DKO+BSA). The skin cholesterol was also massively reduced, with inflammatory cell infiltration in the skin reduced compared to DKO+BSA. The LN Treg population was increased even further compared to DKO+BSA. This increase, however, was different than that seen in DKO+BSA mice because it also resulted in a decrease in cellular activation. These data indicate that apoA-I is effective in improving the Treg response in autoimmune mice, preventing autoimmunity. We have identified apoA-I as potential mechanistic link between atherosclerosis and autoimmunity. ApoA-I treatment prevented cholesterol accumulation and improved the Treg response in DKO mice, thus preventing autoimmunity. Therefore, treatment with apoA-I to increase HDL levels may be an important option to consider when devising treatments for both atherosclerosis and autoimmunity.","abstract_html":"The goal of this work was to examine the role of apoA-I in atherosclerosis and autoimmunity. We used a mouse model lacking the LDL receptor and the apoA-I gene (LDLr-/-,ApoA-I-/- or DKO). LDLr-/- (SKO) mice were used as controls. When fed a cholesterol-containing diet, DKO mice exhibited cholesterol accumulation in the skin and skin-draining lymph nodes (LNs). The LN total cell number was increased, with expansion of T cell, B cell, dendritic cell (DC) and macrophage populations. Interestingly, DKO LN T cells, B cells and DCs had increased cholesterol compared to controls. DKO LN T cells had increased expression of activation markers and proliferation of CD4+CD44high T cells was increased. Plasma autoantibodies were also increased. We concluded that, in the absence of apoA-I, diet-fed DKO mice develop an autoimmune phenotype. These data suggest that apoA-I can modulate immune cell function by regulating cellular cholesterol balance. This, in turn, prevents LN cell expansion, activation and the progression of atherosclerosis. Regulatory T cells (Treg) were increased in LNs of DKO mice. To determine the direct effects of apoA-I on this cell population and the autoimmune phenotype, mice were fed diet for 6 weeks then apoA-I injections began and continued every 48 hours for an additional 6 weeks. After 12 weeks total on diet, apoA-I-treated DKO mice (DKO+A-I) had reduced LN size and reduced LN cell number compared to DKO mice treated with BSA (DKO+BSA). The skin cholesterol was also massively reduced, with inflammatory cell infiltration in the skin reduced compared to DKO+BSA. The LN Treg population was increased even further compared to DKO+BSA. This increase, however, was different than that seen in DKO+BSA mice because it also resulted in a decrease in cellular activation. These data indicate that apoA-I is effective in improving the Treg response in autoimmune mice, preventing autoimmunity. We have identified apoA-I as potential mechanistic link between atherosclerosis and autoimmunity. ApoA-I treatment prevented cholesterol accumulation and improved the Treg response in DKO mice, thus preventing autoimmunity. Therefore, treatment with apoA-I to increase HDL levels may be an important option to consider when devising treatments for both atherosclerosis and autoimmunity.","abstract_has_math":false,"creators":["Wilhelm, Ashley"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-05-06T16:25:03Z","date_published":"2010-05-06T16:25:03Z","updated_at":"2026-07-27T22:01:07Z","subjects":["Immunology"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/14872","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Wilhelm, Ashley"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-05-06T16:25:03Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-05-06T16:25:03Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-05-06T16:25:03Z"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology"]}]},{"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":["http://hdl.handle.net/10339/14872"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The goal of this work was to examine the role of apoA-I in atherosclerosis and autoimmunity. We used a mouse model lacking the LDL receptor and the apoA-I gene (LDLr-/-,ApoA-I-/- or DKO). LDLr-/- (SKO) mice were used as controls. When fed a cholesterol-containing diet, DKO mice exhibited cholesterol accumulation in the skin and skin-draining lymph nodes (LNs). The LN total cell number was increased, with expansion of T cell, B cell, dendritic cell (DC) and macrophage populations. Interestingly, DKO LN T cells, B cells and DCs had increased cholesterol compared to controls. DKO LN T cells had increased expression of activation markers and proliferation of CD4+CD44high T cells was increased. Plasma autoantibodies were also increased. We concluded that, in the absence of apoA-I, diet-fed DKO mice develop an autoimmune phenotype. These data suggest that apoA-I can modulate immune cell function by regulating cellular cholesterol balance. This, in turn, prevents LN cell expansion, activation and the progression of atherosclerosis. Regulatory T cells (Treg) were increased in LNs of DKO mice. To determine the direct effects of apoA-I on this cell population and the autoimmune phenotype, mice were fed diet for 6 weeks then apoA-I injections began and continued every 48 hours for an additional 6 weeks. After 12 weeks total on diet, apoA-I-treated DKO mice (DKO+A-I) had reduced LN size and reduced LN cell number compared to DKO mice treated with BSA (DKO+BSA). The skin cholesterol was also massively reduced, with inflammatory cell infiltration in the skin reduced compared to DKO+BSA. The LN Treg population was increased even further compared to DKO+BSA. This increase, however, was different than that seen in DKO+BSA mice because it also resulted in a decrease in cellular activation. These data indicate that apoA-I is effective in improving the Treg response in autoimmune mice, preventing autoimmunity. We have identified apoA-I as potential mechanistic link between atherosclerosis and autoimmunity. ApoA-I treatment prevented cholesterol accumulation and improved the Treg response in DKO mice, thus preventing autoimmunity. Therefore, treatment with apoA-I to increase HDL levels may be an important option to consider when devising treatments for both atherosclerosis and autoimmunity."]},{"key":"dc:title","label":"Title","values":["The Role of Apolipoprotein A-I in the Modulation of Cholesterol and Immune Homeostasis"]}]}],"canonical_facts":{"dc:creator":["Wilhelm, Ashley"],"dc:date.accessioned":["2010-05-06T16:25:03Z"],"dc:date.available":["2010-05-06T16:25:03Z"],"dc:date.issued":["2010-05-06T16:25:03Z"],"dc:description.abstract":["The goal of this work was to examine the role of apoA-I in atherosclerosis and autoimmunity. We used a mouse model lacking the LDL receptor and the apoA-I gene (LDLr-/-,ApoA-I-/- or DKO). LDLr-/- (SKO) mice were used as controls. When fed a cholesterol-containing diet, DKO mice exhibited cholesterol accumulation in the skin and skin-draining lymph nodes (LNs). The LN total cell number was increased, with expansion of T cell, B cell, dendritic cell (DC) and macrophage populations. Interestingly, DKO LN T cells, B cells and DCs had increased cholesterol compared to controls. DKO LN T cells had increased expression of activation markers and proliferation of CD4+CD44high T cells was increased. Plasma autoantibodies were also increased. We concluded that, in the absence of apoA-I, diet-fed DKO mice develop an autoimmune phenotype. These data suggest that apoA-I can modulate immune cell function by regulating cellular cholesterol balance. This, in turn, prevents LN cell expansion, activation and the progression of atherosclerosis. Regulatory T cells (Treg) were increased in LNs of DKO mice. To determine the direct effects of apoA-I on this cell population and the autoimmune phenotype, mice were fed diet for 6 weeks then apoA-I injections began and continued every 48 hours for an additional 6 weeks. After 12 weeks total on diet, apoA-I-treated DKO mice (DKO+A-I) had reduced LN size and reduced LN cell number compared to DKO mice treated with BSA (DKO+BSA). The skin cholesterol was also massively reduced, with inflammatory cell infiltration in the skin reduced compared to DKO+BSA. The LN Treg population was increased even further compared to DKO+BSA. This increase, however, was different than that seen in DKO+BSA mice because it also resulted in a decrease in cellular activation. These data indicate that apoA-I is effective in improving the Treg response in autoimmune mice, preventing autoimmunity. We have identified apoA-I as potential mechanistic link between atherosclerosis and autoimmunity. ApoA-I treatment prevented cholesterol accumulation and improved the Treg response in DKO mice, thus preventing autoimmunity. Therefore, treatment with apoA-I to increase HDL levels may be an important option to consider when devising treatments for both atherosclerosis and autoimmunity."],"dc:identifier.uri":["http://hdl.handle.net/10339/14872"],"dc:language.iso":["en_US"],"dc:publisher":["Wake Forest University"],"dc:subject":["Immunology"],"dc:title":["The Role of Apolipoprotein A-I in the Modulation of Cholesterol and Immune Homeostasis"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T22:01:07Z"}