{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:51506"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:51506","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"The role of dendritic cells and their chemokine TARC in the pathogenesis of atherosclerosis","abstract":"In this study, the DC-derived chemokine CCL17 and its role in the pathogenesis of atherosclerosis was investigated. By using a ‘knock-in’ mice expressing a targeted replacement of the Ccl17 gene by eGFP, we observed that CCL17+ DCs belong to a mature subpopulation of cDCs related to the myeloid lineage. Microarray profiling showed no further difference in gene regulation or even intrinsic defects of EGFP+ Ccl17E/E compared with EGFP+ Ccl17E/+ BMDCs. Additionally, normal DC functions such as phagocytosis or migration were not altered in Ccl17 knock-out DCs. In vivo, a network of CD11c+ DCs could be detected in the intima of the vessel wall of naïve wt mice, but these cells did not express CCL17, in contrast to a prominent expression of MHC-II. However, during plaque development CCL17+ DCs accumulate within inflamed atherosclerotic lesions in Apoe-/- mice. In addition, CCL17+ DCs were detected in lesions of bone marrow transplanted mice, indicating that these DCs are recruited from the bone marrow to the site of inflammation. Furthermore, we demonstrated that CCL17-deficiency reduces atherosclerotic plaque formation with a decreased macrophage content in the plaque, while the content of SMCs was increased, indicating a more stable plaque phenotype compared to the phenotype observed in Ccl17+/+ Apoe-/- mice. In line with the findings that CCL17 attracts T cells, we observed that CCL17+ DCs attract CD4+ T cells in vitro and in vivo. In addition, increased numbers of CD3+ T cells were detected in atherosclerotic plaques of Ccl17+/+ Apoe-/- compared with Ccl17E/E Apoe-/- mice. Furthermore, CCL17 seems to be necessary for efficient T cell activation, as higher IL-2 levels were observed in the supernatants of T cells cocultured with CCL17+ BMDCs. Moreover IFN-gamma levels were significantly higher in those cultures, indicating that T cells were primed and polarized in a Th1 specific manner. The difference in cytokine profile was also observed in vivo. In LNs of Ccl17+/+ Apoe-/- mice, Ifn-gamma and Il-17 transcription levels were up-regulated, while the typical Th2 cytokines Il-4 and Il-10 were down-regulated in comparison to Ccl17E/E Apoe-/- mice. Finally, adoptive transfer experiments demonstrated that T cells isolated from Ccl17E/E Apoe-/- mice and injected into Apoe-/- recipient mice act atheroprotective. Lesion development in these animals was significantly reduced when compared with Apoe-/- mice receiving T cells from Ccl17+/+ Apoe-/-. These data open the possibility of achieving therapeutic regression and stabilization of advanced atherosclerotic lesions by targeting CCL17.","abstract_html":"In this study, the DC-derived chemokine CCL17 and its role in the pathogenesis of atherosclerosis was investigated. By using a ‘knock-in’ mice expressing a targeted replacement of the Ccl17 gene by eGFP, we observed that CCL17+ DCs belong to a mature subpopulation of cDCs related to the myeloid lineage. Microarray profiling showed no further difference in gene regulation or even intrinsic defects of EGFP+ Ccl17E/E compared with EGFP+ Ccl17E/+ BMDCs. Additionally, normal DC functions such as phagocytosis or migration were not altered in Ccl17 knock-out DCs. In vivo, a network of CD11c+ DCs could be detected in the intima of the vessel wall of naïve wt mice, but these cells did not express CCL17, in contrast to a prominent expression of MHC-II. However, during plaque development CCL17+ DCs accumulate within inflamed atherosclerotic lesions in Apoe-/- mice. In addition, CCL17+ DCs were detected in lesions of bone marrow transplanted mice, indicating that these DCs are recruited from the bone marrow to the site of inflammation. Furthermore, we demonstrated that CCL17-deficiency reduces atherosclerotic plaque formation with a decreased macrophage content in the plaque, while the content of SMCs was increased, indicating a more stable plaque phenotype compared to the phenotype observed in Ccl17+/+ Apoe-/- mice. In line with the findings that CCL17 attracts T cells, we observed that CCL17+ DCs attract CD4+ T cells in vitro and in vivo. In addition, increased numbers of CD3+ T cells were detected in atherosclerotic plaques of Ccl17+/+ Apoe-/- compared with Ccl17E/E Apoe-/- mice. Furthermore, CCL17 seems to be necessary for efficient T cell activation, as higher IL-2 levels were observed in the supernatants of T cells cocultured with CCL17+ BMDCs. Moreover IFN-gamma levels were significantly higher in those cultures, indicating that T cells were primed and polarized in a Th1 specific manner. The difference in cytokine profile was also observed in vivo. In LNs of Ccl17+/+ Apoe-/- mice, Ifn-gamma and Il-17 transcription levels were up-regulated, while the typical Th2 cytokines Il-4 and Il-10 were down-regulated in comparison to Ccl17E/E Apoe-/- mice. Finally, adoptive transfer experiments demonstrated that T cells isolated from Ccl17E/E Apoe-/- mice and injected into Apoe-/- recipient mice act atheroprotective. Lesion development in these animals was significantly reduced when compared with Apoe-/- mice receiving T cells from Ccl17+/+ Apoe-/-. These data open the possibility of achieving therapeutic regression and stabilization of advanced atherosclerotic lesions by targeting CCL17.","abstract_has_math":false,"creators":["Meiler, Svenja"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Weber, Christian"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010","date_published":"2010","updated_at":"2026-07-30T19:40:42Z","subjects":["info:eu-repo/classification/ddc/570","Arteriosklerose","Biowissenschaften, Biologie","Dendritische Zellen","CCL17","Th1","artherosclerosis","dendritic cells"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113793%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113793%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113793%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/51506","outbound_label":"Repository record","outbound_source":"dc:identifier"},"source_record":{"url":"https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51506","prefix":"oai_dc"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Weber, Christian"]},{"key":"dc:creator","label":"Author","values":["Meiler, Svenja"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2010"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-31194"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/570","Arteriosklerose","Biowissenschaften, Biologie","Dendritische Zellen","CCL17","Th1","artherosclerosis","dendritic cells"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/51506","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113793%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["In this study, the DC-derived chemokine CCL17 and its role in the pathogenesis of atherosclerosis was investigated. By using a ‘knock-in’ mice expressing a targeted replacement of the Ccl17 gene by eGFP, we observed that CCL17+ DCs belong to a mature subpopulation of cDCs related to the myeloid lineage. Microarray profiling showed no further difference in gene regulation or even intrinsic defects of EGFP+ Ccl17E/E compared with EGFP+ Ccl17E/+ BMDCs. Additionally, normal DC functions such as phagocytosis or migration were not altered in Ccl17 knock-out DCs. In vivo, a network of CD11c+ DCs could be detected in the intima of the vessel wall of naïve wt mice, but these cells did not express CCL17, in contrast to a prominent expression of MHC-II. However, during plaque development CCL17+ DCs accumulate within inflamed atherosclerotic lesions in Apoe-/- mice. In addition, CCL17+ DCs were detected in lesions of bone marrow transplanted mice, indicating that these DCs are recruited from the bone marrow to the site of inflammation. Furthermore, we demonstrated that CCL17-deficiency reduces atherosclerotic plaque formation with a decreased macrophage content in the plaque, while the content of SMCs was increased, indicating a more stable plaque phenotype compared to the phenotype observed in Ccl17+/+ Apoe-/- mice. In line with the findings that CCL17 attracts T cells, we observed that CCL17+ DCs attract CD4+ T cells in vitro and in vivo. In addition, increased numbers of CD3+ T cells were detected in atherosclerotic plaques of Ccl17+/+ Apoe-/- compared with Ccl17E/E Apoe-/- mice. Furthermore, CCL17 seems to be necessary for efficient T cell activation, as higher IL-2 levels were observed in the supernatants of T cells cocultured with CCL17+ BMDCs. Moreover IFN-gamma levels were significantly higher in those cultures, indicating that T cells were primed and polarized in a Th1 specific manner. The difference in cytokine profile was also observed in vivo. In LNs of Ccl17+/+ Apoe-/- mice, Ifn-gamma and Il-17 transcription levels were up-regulated, while the typical Th2 cytokines Il-4 and Il-10 were down-regulated in comparison to Ccl17E/E Apoe-/- mice. Finally, adoptive transfer experiments demonstrated that T cells isolated from Ccl17E/E Apoe-/- mice and injected into Apoe-/- recipient mice act atheroprotective. Lesion development in these animals was significantly reduced when compared with Apoe-/- mice receiving T cells from Ccl17+/+ Apoe-/-. These data open the possibility of achieving therapeutic regression and stabilization of advanced atherosclerotic lesions by targeting CCL17."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University VI, 89 S. : Ill., graph. Darst. (2010). = Aachen, Techn. Hochsch., Diss., 2010"]},{"key":"dc:title","label":"Title","values":["The role of dendritic cells and their chemokine TARC in the pathogenesis of atherosclerosis"]}]}],"canonical_facts":{"dc:contributor":["Weber, Christian"],"dc:coverage":["DE"],"dc:creator":["Meiler, Svenja"],"dc:date":["2010"],"dc:description":["In this study, the DC-derived chemokine CCL17 and its role in the pathogenesis of atherosclerosis was investigated. By using a ‘knock-in’ mice expressing a targeted replacement of the Ccl17 gene by eGFP, we observed that CCL17+ DCs belong to a mature subpopulation of cDCs related to the myeloid lineage. Microarray profiling showed no further difference in gene regulation or even intrinsic defects of EGFP+ Ccl17E/E compared with EGFP+ Ccl17E/+ BMDCs. Additionally, normal DC functions such as phagocytosis or migration were not altered in Ccl17 knock-out DCs. In vivo, a network of CD11c+ DCs could be detected in the intima of the vessel wall of naïve wt mice, but these cells did not express CCL17, in contrast to a prominent expression of MHC-II. However, during plaque development CCL17+ DCs accumulate within inflamed atherosclerotic lesions in Apoe-/- mice. In addition, CCL17+ DCs were detected in lesions of bone marrow transplanted mice, indicating that these DCs are recruited from the bone marrow to the site of inflammation. Furthermore, we demonstrated that CCL17-deficiency reduces atherosclerotic plaque formation with a decreased macrophage content in the plaque, while the content of SMCs was increased, indicating a more stable plaque phenotype compared to the phenotype observed in Ccl17+/+ Apoe-/- mice. In line with the findings that CCL17 attracts T cells, we observed that CCL17+ DCs attract CD4+ T cells in vitro and in vivo. In addition, increased numbers of CD3+ T cells were detected in atherosclerotic plaques of Ccl17+/+ Apoe-/- compared with Ccl17E/E Apoe-/- mice. Furthermore, CCL17 seems to be necessary for efficient T cell activation, as higher IL-2 levels were observed in the supernatants of T cells cocultured with CCL17+ BMDCs. Moreover IFN-gamma levels were significantly higher in those cultures, indicating that T cells were primed and polarized in a Th1 specific manner. The difference in cytokine profile was also observed in vivo. In LNs of Ccl17+/+ Apoe-/- mice, Ifn-gamma and Il-17 transcription levels were up-regulated, while the typical Th2 cytokines Il-4 and Il-10 were down-regulated in comparison to Ccl17E/E Apoe-/- mice. Finally, adoptive transfer experiments demonstrated that T cells isolated from Ccl17E/E Apoe-/- mice and injected into Apoe-/- recipient mice act atheroprotective. Lesion development in these animals was significantly reduced when compared with Apoe-/- mice receiving T cells from Ccl17+/+ Apoe-/-. These data open the possibility of achieving therapeutic regression and stabilization of advanced atherosclerotic lesions by targeting CCL17."],"dc:identifier":["https://publications.rwth-aachen.de/record/51506","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113793%22"],"dc:language":["eng"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-31194"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University VI, 89 S. : Ill., graph. Darst. (2010). = Aachen, Techn. Hochsch., Diss., 2010"],"dc:subject":["info:eu-repo/classification/ddc/570","Arteriosklerose","Biowissenschaften, Biologie","Dendritische Zellen","CCL17","Th1","artherosclerosis","dendritic cells"],"dc:title":["The role of dendritic cells and their chemokine TARC in the pathogenesis of atherosclerosis"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:40:42Z"}