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We tested whether adoptive cell therapy (ACT) with Tregulatory cells (Tregs), engineered to selectively migrate in the atherosclerotic plaque, would dampen the immune-inflammatory response in the arterial wall in animal models of familial hypercholesterolaemia (FH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>FH patients presented a decreased Treg suppressive function associated to an increased inflammatory burden. A similar phenotype was observed in Ldlr \u2212\/\u2212 mice accompanied by a selective increased expression of the chemokine CX3CL1 in the aorta but not in other districts (lymph nodes, spleen, and liver). Treg overexpressing CX3CR1 were thus generated (CX3CR1+-Tregs) to drive Tregs selectively to the plaque. CX3CR1+-Tregs were injected (i.v.) in Ldlr \u2212\/\u2212 fed high-cholesterol diet (western type diet, WTD) for 8\u2009weeks. CX3CR1+-Tregs were detected in the aorta, but not in other tissues, of Ldlr \u2212\/\u2212 mice 24\u2009h after ACT, corroborating the efficacy of this approach. After 4 additional weeks of WTD, ACT with CX3CR1+-Tregs resulted in reduced plaque progression and lipid deposition, ameliorated plaque stability by increasing collagen and smooth muscle cells content, while decreasing the number of pro-inflammatory macrophages. Shotgun proteomics of the aorta showed a metabolic rewiring in CX3CR1+-Tregs treated Ldlr \u2212\/\u2212 mice compared to controls that was associated with the improvement of inflammation-resolving pathways and disease progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ACT with vasculotropic Tregs appears as a promising strategy to selectively target immune activation in the atherosclerotic plaque.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa264","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T19:14:13Z","timestamp":1599160453000},"page":"2069-2082","source":"Crossref","is-referenced-by-count":43,"title":["Adoptive transfer of CX3CR1 transduced-T regulatory cells improves homing to the atherosclerotic plaques and dampens atherosclerosis progression"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-1177","authenticated-orcid":false,"given":"Fabrizia","family":"Bonacina","sequence":"first","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Martini","sequence":"additional","affiliation":[{"name":"Adaptive Immunity Lab, Humanitas Clinical and Research Center, Rozzano\u2014IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Svecla","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9006-6542","authenticated-orcid":false,"given":"Jasmine","family":"Nour","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-2186","authenticated-orcid":false,"given":"Marco","family":"Cremonesi","sequence":"additional","affiliation":[{"name":"Adaptive Immunity Lab, Humanitas Clinical and Research Center, Rozzano\u2014IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-0857","authenticated-orcid":false,"given":"Giangiacomo","family":"Beretta","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Policy, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Moregola","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Pellegatta","sequence":"additional","affiliation":[{"name":"IRCCS Multimedica, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-3099","authenticated-orcid":false,"given":"Veronica","family":"Zampoleri","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"},{"name":"Centro SISA per lo Studio dell\u2019Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-2094","authenticated-orcid":false,"given":"Alberico Luigi","family":"Catapano","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"},{"name":"IRCCS Multimedica, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-3368","authenticated-orcid":false,"given":"Marinos","family":"Kallikourdis","sequence":"additional","affiliation":[{"name":"Adaptive Immunity Lab, Humanitas Clinical and Research Center, Rozzano\u2014IRCCS, Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-1257","authenticated-orcid":false,"given":"Giuseppe Danilo","family":"Norata","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"},{"name":"Centro SISA per lo Studio dell\u2019Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2021072816521367800_cvaa264-B1","volume-title":"Familial hypercholesterolemia: genes and beyond","author":"Warden","year":"2000"},{"key":"2021072816521367800_cvaa264-B2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3389\/fphar.2018.00707","article-title":"Familial hypercholesterolemia: new horizons for diagnosis and effective management","volume":"9","author":"Mytilinaiou","year":"2018","journal-title":"Front 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