The Autoimmune Regulator (Aire) Confers Immunosuppressive Properties to Dendritic Cells

Hdl Handle:
http://hdl.handle.net/10675.2/345136
Title:
The Autoimmune Regulator (Aire) Confers Immunosuppressive Properties to Dendritic Cells
Authors:
Eisenman, Daniel
Abstract:
The Autoimmune regulator (Aire) is a transcription factor that controls expression of self antigens by thymic epithelium and it plays a critical role in the deletion of autoreactive thymocytes and prevention of autoimmunity. Recent studies have reported Aire expression in dendritic cells (DC) located in spleen and lymph nodes, suggesting a role for Aire in extra-thymic tolerance induction. Molecular and functional studies conducted in this dissertation revealed that Aire induction in bone marrow derived DC results in expression of immunosuppressive cytokines and decreased expression of co-stimulatory molecules. Similar results were also obtained from lenti-virus-mediated Aire overexpression in the DC2.4 dendritic cell line. It was further shown that DC from Aire'7' mice exhibited greater antigen presenting function both in vitro and in vivo. These DC were more potent stimulators of T cell proliferation leading to increased IL-2 and IFNy production. These studies suggest that Aire7' DC may play a role in exacerbating the autoimmunity seen in Aire7' mice. DC over-expressing Aire were shown to suppress activation and proliferation of naive T cells and promote activation-induced cell death of activated T cells. Furthermore, we demonstrate that Aire also controls transcription of tissue-specific antigens in DC. These results, together, suggest that Aire plays an important role in the tolerogenic function of DC.
Affiliation:
Center for Biotechnology and Genomic Medicine
Issue Date:
May-2007
URI:
http://hdl.handle.net/10675.2/345136
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304784922?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorEisenman, Danielen
dc.date.accessioned2015-02-23T21:32:20Z-
dc.date.available2015-02-23T21:32:20Z-
dc.date.issued2007-05-
dc.identifier.urihttp://hdl.handle.net/10675.2/345136-
dc.description.abstractThe Autoimmune regulator (Aire) is a transcription factor that controls expression of self antigens by thymic epithelium and it plays a critical role in the deletion of autoreactive thymocytes and prevention of autoimmunity. Recent studies have reported Aire expression in dendritic cells (DC) located in spleen and lymph nodes, suggesting a role for Aire in extra-thymic tolerance induction. Molecular and functional studies conducted in this dissertation revealed that Aire induction in bone marrow derived DC results in expression of immunosuppressive cytokines and decreased expression of co-stimulatory molecules. Similar results were also obtained from lenti-virus-mediated Aire overexpression in the DC2.4 dendritic cell line. It was further shown that DC from Aire'7' mice exhibited greater antigen presenting function both in vitro and in vivo. These DC were more potent stimulators of T cell proliferation leading to increased IL-2 and IFNy production. These studies suggest that Aire7' DC may play a role in exacerbating the autoimmunity seen in Aire7' mice. DC over-expressing Aire were shown to suppress activation and proliferation of naive T cells and promote activation-induced cell death of activated T cells. Furthermore, we demonstrate that Aire also controls transcription of tissue-specific antigens in DC. These results, together, suggest that Aire plays an important role in the tolerogenic function of DC.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304784922?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectAireen
dc.subjectAutoimmune Regulatoren
dc.subjectdendritic cellen
dc.subjectT Cell Toleranceen
dc.subjectAutoimmunityen
dc.subjectTissue Specific Antigensen
dc.subjectPromiscuous Gene Expressionen
dc.subjectImmune Regulationen
dc.titleThe Autoimmune Regulator (Aire) Confers Immunosuppressive Properties to Dendritic Cellsen
dc.typeDissertationen
dc.contributor.departmentCenter for Biotechnology and Genomic Medicineen
dc.description.advisorShe, Jin-Xiongen
dc.description.committeeMcIndoe, Richard A.; Wang, Cong-yi; Mi, Qing-Sheng; Muir, Andrew; Ignatowicz, Leszek; Podolsky, Roberten
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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