{"id":{"repo_id":"birmingham","oai_identifier":"oai:etheses.bham.ac.uk:1551"},"canonical_url":"https://search.dev.ndltd.org/etd/birmingham/oai:etheses.bham.ac.uk:1551","repository":{"repo_id":"birmingham","name":"University of Birmingham","base_url":"https://etheses.bham.ac.uk/cgi/oai2"},"display":{"title":"Studies on the differentiation of inflammatory and regulatory T-cells","abstract":"Low vitamin D is associated with an increased risk of autoimmune diseases, whose pathology might involve T\\(_R\\)\\(_e\\)\\(_g\\) and T\\(_h\\)17 dysregulation. Thus, understanding how vitamin D modifies CD4\\(^+\\) T-cell responses holds therapeutic potential. I therefore investigated the effect of 1,25(OH)\\(_2\\)D\\(_3\\), the active form of vitamin D, upon human CD4\\(^+\\) T-cell differentiation. 1,25(OH)\\(_2\\)D\\(_3\\), acted directly upon human CD4\\(^+\\) T-cells, suppressing inflammatory cytokines (IL-17, IL-21, IFN\\(_y\\) and IL-22) whilst enhancing regulatory markers (CTLA-4, CD25, FoxP3 and IL-10). Consistently, 1,25(OH)\\(_2\\)D\\(_3\\)-treated T-cells suppressed division of naive T-cells stimulated by dendritic cells (DCs). Strong up-regulation of CTLA-4 by 1,25(OH)\\(_2\\)D\\(_3\\)reduced B7 expression by DCs, suggesting that enhanced CTLA-4 could be important mechanistically in 1,25(OH)\\(_2\\)D\\(_3\\)modified immunity. Furthermore, pro-regulatory effects of 1,25(OH)\\(_2\\)D\\(_3\\)were maintained under inflammatory conditions and modest suppression of established IL-17 by 1,25(OH)\\(_2\\)D\\(_3\\) was observed, supporting ability of 1,25(OH)\\(_2\\)D\\(_3\\)to control T-cell phenotype at inflammatory sites. DCs could also efficiently convert 25(OH)D\\(_3\\)to drive 1,25(OH)\\(_2\\)D\\(_3\\)-modified T-cell responses, which might be important in-vivo, given the low level of 1,25(OH)\\(_2\\)D\\(_3\\)in serum. Whether dysregulation of the T\\(_R\\)\\(_e\\)\\(_g\\)/T17 balance or response to 1,25(OH)\\(_2\\)D\\(_3\\) was associated with disease outcome in early synovitis patients was also studied. Although the TReg/T17 ratio did not stratify with outcome, T-cell responses to 1,25(OH)\\(_2\\)D\\(_3\\) were observed in all patients, suggesting that their VDR signalling is intact and that 1,25(OH)\\(_2\\)D\\(_3\\)might be useful in the treatment of synovitis.","abstract_html":"Low vitamin D is associated with an increased risk of autoimmune diseases, whose pathology might involve T<span class=\"etd-inline-math\"><sub>R</sub></span><span class=\"etd-inline-math\"><sub>e</sub></span><span class=\"etd-inline-math\"><sub>g</sub></span> and T<span class=\"etd-inline-math\"><sub>h</sub></span>17 dysregulation. Thus, understanding how vitamin D modifies CD4<span class=\"etd-inline-math\"><sup>+</sup></span> T-cell responses holds therapeutic potential. I therefore investigated the effect of 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>, the active form of vitamin D, upon human CD4<span class=\"etd-inline-math\"><sup>+</sup></span> T-cell differentiation. 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>, acted directly upon human CD4<span class=\"etd-inline-math\"><sup>+</sup></span> T-cells, suppressing inflammatory cytokines (IL-17, IL-21, IFN<span class=\"etd-inline-math\"><sub>y</sub></span> and IL-22) whilst enhancing regulatory markers (CTLA-4, CD25, FoxP3 and IL-10). Consistently, 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>-treated T-cells suppressed division of naive T-cells stimulated by dendritic cells (DCs). Strong up-regulation of CTLA-4 by 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>reduced B7 expression by DCs, suggesting that enhanced CTLA-4 could be important mechanistically in 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>modified immunity. Furthermore, pro-regulatory effects of 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>were maintained under inflammatory conditions and modest suppression of established IL-17 by 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span> was observed, supporting ability of 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>to control T-cell phenotype at inflammatory sites. DCs could also efficiently convert 25(OH)D<span class=\"etd-inline-math\"><sub>3</sub></span>to drive 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>-modified T-cell responses, which might be important in-vivo, given the low level of 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>in serum. Whether dysregulation of the T<span class=\"etd-inline-math\"><sub>R</sub></span><span class=\"etd-inline-math\"><sub>e</sub></span><span class=\"etd-inline-math\"><sub>g</sub></span>/T17 balance or response to 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span> was associated with disease outcome in early synovitis patients was also studied. Although the TReg/T17 ratio did not stratify with outcome, T-cell responses to 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span> were observed in all patients, suggesting that their VDR signalling is intact and that 1,25(OH)<span class=\"etd-inline-math\"><sub>2</sub></span>D<span class=\"etd-inline-math\"><sub>3</sub></span>might be useful in the treatment of synovitis.","abstract_has_math":true,"creators":["Jeffery, Louisa Elizabeth"],"institution":"University of Birmingham","degree_name":"d_ph","degree_level":"d_ph","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-12","date_published":"2012-12","updated_at":"2026-07-24T01:11:37Z","subjects":["RC Internal medicine","RA Public aspects of medicine"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["va"]},{"key":"dc:creator","label":"Author","values":["Jeffery, Louisa Elizabeth"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-12"]},{"key":"dc:date.issued","label":"Date","values":["2012-12"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["College of Medical & Dental Sciences","School of Immunity and Infection"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Birmingham"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["http://etheses.bham.ac.uk//id/eprint/1551/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["d_ph"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["d_ph"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["RC Internal medicine","RA Public aspects of medicine"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://etheses.bham.ac.uk//id/eprint/1551/1/Decl_IS_Jeffery_11_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1551/11/Jeffery_12_PhD.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Low vitamin D is associated with an increased risk of autoimmune diseases, whose pathology might involve T\\(_R\\)\\(_e\\)\\(_g\\) and T\\(_h\\)17 dysregulation. Thus, understanding how vitamin D modifies CD4\\(^+\\) T-cell responses holds therapeutic potential. I therefore investigated the effect of 1,25(OH)\\(_2\\)D\\(_3\\), the active form of vitamin D, upon human CD4\\(^+\\) T-cell differentiation. 1,25(OH)\\(_2\\)D\\(_3\\), acted directly upon human CD4\\(^+\\) T-cells, suppressing inflammatory cytokines (IL-17, IL-21, IFN\\(_y\\) and IL-22) whilst enhancing regulatory markers (CTLA-4, CD25, FoxP3 and IL-10). Consistently, 1,25(OH)\\(_2\\)D\\(_3\\)-treated T-cells suppressed division of naive T-cells stimulated by dendritic cells (DCs). Strong up-regulation of CTLA-4 by 1,25(OH)\\(_2\\)D\\(_3\\)reduced B7 expression by DCs, suggesting that enhanced CTLA-4 could be important mechanistically in 1,25(OH)\\(_2\\)D\\(_3\\)modified immunity. Furthermore, pro-regulatory effects of 1,25(OH)\\(_2\\)D\\(_3\\)were maintained under inflammatory conditions and modest suppression of established IL-17 by 1,25(OH)\\(_2\\)D\\(_3\\) was observed, supporting ability of 1,25(OH)\\(_2\\)D\\(_3\\)to control T-cell phenotype at inflammatory sites. DCs could also efficiently convert 25(OH)D\\(_3\\)to drive 1,25(OH)\\(_2\\)D\\(_3\\)-modified T-cell responses, which might be important in-vivo, given the low level of 1,25(OH)\\(_2\\)D\\(_3\\)in serum. Whether dysregulation of the T\\(_R\\)\\(_e\\)\\(_g\\)/T17 balance or response to 1,25(OH)\\(_2\\)D\\(_3\\) was associated with disease outcome in early synovitis patients was also studied. Although the TReg/T17 ratio did not stratify with outcome, T-cell responses to 1,25(OH)\\(_2\\)D\\(_3\\) were observed in all patients, suggesting that their VDR signalling is intact and that 1,25(OH)\\(_2\\)D\\(_3\\)might be useful in the treatment of synovitis."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Studies on the differentiation of inflammatory and regulatory T-cells"]}]}],"canonical_facts":{"dc:contributor.sponsor":["va"],"dc:creator":["Jeffery, Louisa Elizabeth"],"dc:date":["2012-12"],"dc:date.issued":["2012-12"],"dc:description.abstract":["Low vitamin D is associated with an increased risk of autoimmune diseases, whose pathology might involve T\\(_R\\)\\(_e\\)\\(_g\\) and T\\(_h\\)17 dysregulation. Thus, understanding how vitamin D modifies CD4\\(^+\\) T-cell responses holds therapeutic potential. I therefore investigated the effect of 1,25(OH)\\(_2\\)D\\(_3\\), the active form of vitamin D, upon human CD4\\(^+\\) T-cell differentiation. 1,25(OH)\\(_2\\)D\\(_3\\), acted directly upon human CD4\\(^+\\) T-cells, suppressing inflammatory cytokines (IL-17, IL-21, IFN\\(_y\\) and IL-22) whilst enhancing regulatory markers (CTLA-4, CD25, FoxP3 and IL-10). Consistently, 1,25(OH)\\(_2\\)D\\(_3\\)-treated T-cells suppressed division of naive T-cells stimulated by dendritic cells (DCs). Strong up-regulation of CTLA-4 by 1,25(OH)\\(_2\\)D\\(_3\\)reduced B7 expression by DCs, suggesting that enhanced CTLA-4 could be important mechanistically in 1,25(OH)\\(_2\\)D\\(_3\\)modified immunity. Furthermore, pro-regulatory effects of 1,25(OH)\\(_2\\)D\\(_3\\)were maintained under inflammatory conditions and modest suppression of established IL-17 by 1,25(OH)\\(_2\\)D\\(_3\\) was observed, supporting ability of 1,25(OH)\\(_2\\)D\\(_3\\)to control T-cell phenotype at inflammatory sites. DCs could also efficiently convert 25(OH)D\\(_3\\)to drive 1,25(OH)\\(_2\\)D\\(_3\\)-modified T-cell responses, which might be important in-vivo, given the low level of 1,25(OH)\\(_2\\)D\\(_3\\)in serum. Whether dysregulation of the T\\(_R\\)\\(_e\\)\\(_g\\)/T17 balance or response to 1,25(OH)\\(_2\\)D\\(_3\\) was associated with disease outcome in early synovitis patients was also studied. Although the TReg/T17 ratio did not stratify with outcome, T-cell responses to 1,25(OH)\\(_2\\)D\\(_3\\) were observed in all patients, suggesting that their VDR signalling is intact and that 1,25(OH)\\(_2\\)D\\(_3\\)might be useful in the treatment of synovitis."],"dc:format":["application/pdf"],"dc:identifier.uri":["http://etheses.bham.ac.uk//id/eprint/1551/1/Decl_IS_Jeffery_11_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1551/11/Jeffery_12_PhD.pdf"],"dc:publisher.department":["College of Medical & Dental Sciences","School of Immunity and Infection"],"dc:publisher.institution":["University of Birmingham"],"dc:relation.isreferencedby":["http://etheses.bham.ac.uk//id/eprint/1551/"],"dc:subject":["RC Internal medicine","RA Public aspects of medicine"],"dc:title":["Studies on the differentiation of inflammatory and regulatory T-cells"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["d_ph"],"dc:type.qualificationname":["d_ph"]},"updated_at":"2026-07-24T01:11:37Z"}