{"id":{"repo_id":"wustl","oai_identifier":"oai:openscholarship.wustl.edu:etd-1429"},"canonical_url":"https://search.dev.ndltd.org/etd/wustl/oai:openscholarship.wustl.edu:etd-1429","repository":{"repo_id":"wustl","name":"Washington University in St. Louis","base_url":"https://openscholarship.wustl.edu/do/oai/"},"display":{"title":"Batf regulates previously unknown AP-1 target genes to control TH17 differentiation","abstract":"Activator protein 1: AP-1) transcription factors are dimers of Jun, Fos, musculoaponeurotic fibrosarcoma: MAF) and activating transcription factor: ATF) family proteins that are characterized by a basic region and a leucine zipper domain. While many AP-1 proteins also contain defined transcriptional activation domains: TADs), some consist only of a basic region and leucine zipper and are thought to function as inhibitors of AP-1 activity. We found that the AP-1 protein Batf, which lacks a TAD, is highly expressed in T helper cells compared to various other immune cells and tissues. IL-17-producing T helper: TH17) cells are a CD4+ T cell subset that coordinates inflammatory responses in host defense but are pathogenic in autoimmunity. To study the role of Batf in T cells, we generated Batf deficient mice by gene targeting. Batf -/- mice show a highly selective defect in TH17 differentiation. As a result, Batf -/- mice are completely resistant to experimental autoimmune encephalomyelitis. Using gene expression analysis, we found that Batf -/- T cells fail to induce known TH17-specific transcription factors, such as RORγt, and the cytokine IL-21, required for TH17 differentiation. Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf -/- T cells, suggesting that Batf may be required directly for IL-17 transcription. We found that the IL17 promoter is Batf-responsive, and upon TH17 differentiation, Batf binds to several conserved intergenic elements in the IL17A/F locus as well as to regions in the IL17, IL21 and IL22 promoters. Using bio-computational methods we determined that the Batf-binding element in the IL17, IL21 and IL22 promoters differs from canonical symmetric AP-1 elements. Using EMSA analysis we found that Batf forms heterodimers preferentially with JunB during TH17 differentiation. These results demonstrate that the AP-1 factor Batf regulates previously unknown AP-1 target genes to control TH17 differentiation and TH17-mediated autoimmune disease.","abstract_html":"Activator protein 1: AP-1) transcription factors are dimers of Jun, Fos, musculoaponeurotic fibrosarcoma: MAF) and activating transcription factor: ATF) family proteins that are characterized by a basic region and a leucine zipper domain. While many AP-1 proteins also contain defined transcriptional activation domains: TADs), some consist only of a basic region and leucine zipper and are thought to function as inhibitors of AP-1 activity. We found that the AP-1 protein Batf, which lacks a TAD, is highly expressed in T helper cells compared to various other immune cells and tissues. IL-17-producing T helper: TH17) cells are a CD4+ T cell subset that coordinates inflammatory responses in host defense but are pathogenic in autoimmunity. To study the role of Batf in T cells, we generated Batf deficient mice by gene targeting. Batf <super>-/-</super> mice show a highly selective defect in TH17 differentiation. As a result, Batf -/- mice are completely resistant to experimental autoimmune encephalomyelitis. Using gene expression analysis, we found that Batf <super>-/-</super> T cells fail to induce known TH17-specific transcription factors, such as RORγt, and the cytokine IL-21, required for TH17 differentiation. Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf <super>-/-</super> T cells, suggesting that Batf may be required directly for IL-17 transcription. We found that the IL17 promoter is Batf-responsive, and upon TH17 differentiation, Batf binds to several conserved intergenic elements in the IL17A/F locus as well as to regions in the IL17, IL21 and IL22 promoters. Using bio-computational methods we determined that the Batf-binding element in the IL17, IL21 and IL22 promoters differs from canonical symmetric AP-1 elements. Using EMSA analysis we found that Batf forms heterodimers preferentially with JunB during TH17 differentiation. These results demonstrate that the AP-1 factor Batf regulates previously unknown AP-1 target genes to control TH17 differentiation and TH17-mediated autoimmune disease.","abstract_has_math":false,"creators":["Schraml, Barbara"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Immunology","degree_department":null,"school":null,"contributors":["Kenneth Murphy"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-01-01T08:00:00Z","date_published":"2009-01-01T08:00:00Z","updated_at":"2026-07-24T06:13:05Z","subjects":["Health Sciences","Immunology","Batf","Interleukin 17","T helper cell","Th17"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7BG2M0C"],"render_values":[{"text":"https://doi.org/10.7936/K7BG2M0C","href":"https://doi.org/10.7936/K7BG2M0C","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/430","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kenneth Murphy"]},{"key":"dc:creator","label":"Author","values":["Schraml, Barbara"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-05-25T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences","Immunology","Batf","Interleukin 17","T helper cell","Th17"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/430"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7BG2M0C"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Activator protein 1: AP-1) transcription factors are dimers of Jun, Fos, musculoaponeurotic fibrosarcoma: MAF) and activating transcription factor: ATF) family proteins that are characterized by a basic region and a leucine zipper domain. While many AP-1 proteins also contain defined transcriptional activation domains: TADs), some consist only of a basic region and leucine zipper and are thought to function as inhibitors of AP-1 activity. We found that the AP-1 protein Batf, which lacks a TAD, is highly expressed in T helper cells compared to various other immune cells and tissues. IL-17-producing T helper: TH17) cells are a CD4+ T cell subset that coordinates inflammatory responses in host defense but are pathogenic in autoimmunity. To study the role of Batf in T cells, we generated Batf deficient mice by gene targeting. Batf -/- mice show a highly selective defect in TH17 differentiation. As a result, Batf -/- mice are completely resistant to experimental autoimmune encephalomyelitis. Using gene expression analysis, we found that Batf -/- T cells fail to induce known TH17-specific transcription factors, such as RORγt, and the cytokine IL-21, required for TH17 differentiation. Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf -/- T cells, suggesting that Batf may be required directly for IL-17 transcription. We found that the IL17 promoter is Batf-responsive, and upon TH17 differentiation, Batf binds to several conserved intergenic elements in the IL17A/F locus as well as to regions in the IL17, IL21 and IL22 promoters. Using bio-computational methods we determined that the Batf-binding element in the IL17, IL21 and IL22 promoters differs from canonical symmetric AP-1 elements. Using EMSA analysis we found that Batf forms heterodimers preferentially with JunB during TH17 differentiation. These results demonstrate that the AP-1 factor Batf regulates previously unknown AP-1 target genes to control TH17 differentiation and TH17-mediated autoimmune disease."]},{"key":"dc:title","label":"Title","values":["Batf regulates previously unknown AP-1 target genes to control TH17 differentiation"]}]}],"canonical_facts":{"dc:contributor":["Kenneth Murphy"],"dc:creator":["Schraml, Barbara"],"dc:date.available":["2014-05-25T07:00:00Z"],"dc:description.abstract":["Activator protein 1: AP-1) transcription factors are dimers of Jun, Fos, musculoaponeurotic fibrosarcoma: MAF) and activating transcription factor: ATF) family proteins that are characterized by a basic region and a leucine zipper domain. While many AP-1 proteins also contain defined transcriptional activation domains: TADs), some consist only of a basic region and leucine zipper and are thought to function as inhibitors of AP-1 activity. We found that the AP-1 protein Batf, which lacks a TAD, is highly expressed in T helper cells compared to various other immune cells and tissues. IL-17-producing T helper: TH17) cells are a CD4+ T cell subset that coordinates inflammatory responses in host defense but are pathogenic in autoimmunity. To study the role of Batf in T cells, we generated Batf deficient mice by gene targeting. Batf -/- mice show a highly selective defect in TH17 differentiation. As a result, Batf -/- mice are completely resistant to experimental autoimmune encephalomyelitis. Using gene expression analysis, we found that Batf -/- T cells fail to induce known TH17-specific transcription factors, such as RORγt, and the cytokine IL-21, required for TH17 differentiation. Neither addition of IL-21 nor overexpression of RORγt fully restores IL-17 production in Batf -/- T cells, suggesting that Batf may be required directly for IL-17 transcription. We found that the IL17 promoter is Batf-responsive, and upon TH17 differentiation, Batf binds to several conserved intergenic elements in the IL17A/F locus as well as to regions in the IL17, IL21 and IL22 promoters. Using bio-computational methods we determined that the Batf-binding element in the IL17, IL21 and IL22 promoters differs from canonical symmetric AP-1 elements. Using EMSA analysis we found that Batf forms heterodimers preferentially with JunB during TH17 differentiation. These results demonstrate that the AP-1 factor Batf regulates previously unknown AP-1 target genes to control TH17 differentiation and TH17-mediated autoimmune disease."],"dc:identifier":["https://openscholarship.wustl.edu/etd/430"],"dc:identifier.doi":["https://doi.org/10.7936/K7BG2M0C"],"dc:language":["English (en)"],"dc:subject":["Health Sciences","Immunology","Batf","Interleukin 17","T helper cell","Th17"],"dc:title":["Batf regulates previously unknown AP-1 target genes to control TH17 differentiation"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:13:05Z"}