{"id":{"repo_id":"umn","oai_identifier":"oai:conservancy.umn.edu:11299/188891"},"canonical_url":"https://search.dev.ndltd.org/etd/umn/oai:conservancy.umn.edu:11299/188891","repository":{"repo_id":"umn","name":"University of Minnesota","base_url":"https://conservancy.umn.edu/server/oai/request"},"display":{"title":"Analysis of Adenosine 2a Receptors During the Immune Recognition of Foreign and Self-Antigens","abstract":"Purinergic receptors are attractive therapeutic targets that can regulate several facets of the immune system. This dissertation examines the role of purinergic G protein-coupled Adenosine 2a (A2aR) receptors in regulating adaptive immune responses during the primary response to vaccination and during self-antigen recognition in the context autoimmunity. Administration of A2aR agonist CGS-21680 (CGS) can alter CD4 T cell differentiation by diverting helper T cells away from a germinal center follicular helper T cells (GC-Tfh) linage that promotes the survival, differentiation, isotype class-switching, and affinity maturation of B cells. Although GC-Tfh cells are beneficial during the clearance of certain pathogens, they also can be detrimental if they malfunction and mistakenly provide help to pathogenic self-specific B cells. Previous studies suggest that A2aRs acts as a barrier to autoimmunity by limiting inflammatory responses. Our studies support this claim by showing that prophylactic treatment with CGS blocks autoimmune arthritis. A2aR agonist treatment caused a reduction in the frequency and number of pathogenic GC-Tfh cells and isotype class-switched plasmablasts that respond to autoantigen. CGS treatment of mice after the early onset of mild arthritis also had a therapeutic benefit and blocked disease progression. CGS therapy reduced the number pathogenic GC-Tfh cells and autoantibody titers, suggesting that A2aR downstream signals may serve to limit dangerous GC-Tfh cell effectors that contribute to autoimmune disease manifestations, thus making it an attractive target for future immunotherapies.","abstract_html":"Purinergic receptors are attractive therapeutic targets that can regulate several facets of the immune system. This dissertation examines the role of purinergic G protein-coupled Adenosine 2a (A2aR) receptors in regulating adaptive immune responses during the primary response to vaccination and during self-antigen recognition in the context autoimmunity. Administration of A2aR agonist CGS-21680 (CGS) can alter CD4 T cell differentiation by diverting helper T cells away from a germinal center follicular helper T cells (GC-Tfh) linage that promotes the survival, differentiation, isotype class-switching, and affinity maturation of B cells. Although GC-Tfh cells are beneficial during the clearance of certain pathogens, they also can be detrimental if they malfunction and mistakenly provide help to pathogenic self-specific B cells. Previous studies suggest that A2aRs acts as a barrier to autoimmunity by limiting inflammatory responses. Our studies support this claim by showing that prophylactic treatment with CGS blocks autoimmune arthritis. A2aR agonist treatment caused a reduction in the frequency and number of pathogenic GC-Tfh cells and isotype class-switched plasmablasts that respond to autoantigen. CGS treatment of mice after the early onset of mild arthritis also had a therapeutic benefit and blocked disease progression. CGS therapy reduced the number pathogenic GC-Tfh cells and autoantibody titers, suggesting that A2aR downstream signals may serve to limit dangerous GC-Tfh cell effectors that contribute to autoimmune disease manifestations, thus making it an attractive target for future immunotherapies.","abstract_has_math":false,"creators":["Schmiel, Shirdi"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-05","date_published":"2017-05","updated_at":"2026-07-24T05:19:54Z","subjects":["Adenosine","Adenosine 2a Receptor","Follicular Helper T cells","Germinal Centers","Purinergic receptors"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11299/188891","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Schmiel, Shirdi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-07-18T14:38:28Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-07-18T14:38:28Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Adenosine","Adenosine 2a Receptor","Follicular Helper T cells","Germinal Centers","Purinergic receptors"]}]},{"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":["http://hdl.handle.net/11299/188891"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["University of Minnesota Ph.D. dissertation. May 2017. Major: Microbiology, Immunology and Cancer Biology. Advisors: Daniel Mueller, Michael Farrar. 1 computer file (PDF); ix, 92 pages."]},{"key":"dc:description.abstract","label":"Abstract","values":["Purinergic receptors are attractive therapeutic targets that can regulate several facets of the immune system. This dissertation examines the role of purinergic G protein-coupled Adenosine 2a (A2aR) receptors in regulating adaptive immune responses during the primary response to vaccination and during self-antigen recognition in the context autoimmunity. Administration of A2aR agonist CGS-21680 (CGS) can alter CD4 T cell differentiation by diverting helper T cells away from a germinal center follicular helper T cells (GC-Tfh) linage that promotes the survival, differentiation, isotype class-switching, and affinity maturation of B cells. Although GC-Tfh cells are beneficial during the clearance of certain pathogens, they also can be detrimental if they malfunction and mistakenly provide help to pathogenic self-specific B cells. Previous studies suggest that A2aRs acts as a barrier to autoimmunity by limiting inflammatory responses. Our studies support this claim by showing that prophylactic treatment with CGS blocks autoimmune arthritis. A2aR agonist treatment caused a reduction in the frequency and number of pathogenic GC-Tfh cells and isotype class-switched plasmablasts that respond to autoantigen. CGS treatment of mice after the early onset of mild arthritis also had a therapeutic benefit and blocked disease progression. CGS therapy reduced the number pathogenic GC-Tfh cells and autoantibody titers, suggesting that A2aR downstream signals may serve to limit dangerous GC-Tfh cell effectors that contribute to autoimmune disease manifestations, thus making it an attractive target for future immunotherapies."]},{"key":"dc:title","label":"Title","values":["Analysis of Adenosine 2a Receptors During the Immune Recognition of Foreign and Self-Antigens"]}]}],"canonical_facts":{"dc:creator":["Schmiel, Shirdi"],"dc:date.accessioned":["2017-07-18T14:38:28Z"],"dc:date.available":["2017-07-18T14:38:28Z"],"dc:date.issued":["2017-05"],"dc:description":["University of Minnesota Ph.D. dissertation. May 2017. Major: Microbiology, Immunology and Cancer Biology. Advisors: Daniel Mueller, Michael Farrar. 1 computer file (PDF); ix, 92 pages."],"dc:description.abstract":["Purinergic receptors are attractive therapeutic targets that can regulate several facets of the immune system. This dissertation examines the role of purinergic G protein-coupled Adenosine 2a (A2aR) receptors in regulating adaptive immune responses during the primary response to vaccination and during self-antigen recognition in the context autoimmunity. Administration of A2aR agonist CGS-21680 (CGS) can alter CD4 T cell differentiation by diverting helper T cells away from a germinal center follicular helper T cells (GC-Tfh) linage that promotes the survival, differentiation, isotype class-switching, and affinity maturation of B cells. Although GC-Tfh cells are beneficial during the clearance of certain pathogens, they also can be detrimental if they malfunction and mistakenly provide help to pathogenic self-specific B cells. Previous studies suggest that A2aRs acts as a barrier to autoimmunity by limiting inflammatory responses. Our studies support this claim by showing that prophylactic treatment with CGS blocks autoimmune arthritis. A2aR agonist treatment caused a reduction in the frequency and number of pathogenic GC-Tfh cells and isotype class-switched plasmablasts that respond to autoantigen. CGS treatment of mice after the early onset of mild arthritis also had a therapeutic benefit and blocked disease progression. CGS therapy reduced the number pathogenic GC-Tfh cells and autoantibody titers, suggesting that A2aR downstream signals may serve to limit dangerous GC-Tfh cell effectors that contribute to autoimmune disease manifestations, thus making it an attractive target for future immunotherapies."],"dc:identifier.uri":["http://hdl.handle.net/11299/188891"],"dc:language.iso":["en"],"dc:subject":["Adenosine","Adenosine 2a Receptor","Follicular Helper T cells","Germinal Centers","Purinergic receptors"],"dc:title":["Analysis of Adenosine 2a Receptors During the Immune Recognition of Foreign and Self-Antigens"],"dc:type":["Thesis or Dissertation"]},"updated_at":"2026-07-24T05:19:54Z"}