{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:44:30Z","timestamp":1785300270919,"version":"3.55.0"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["PG\/18\/43\/33688"],"award-info":[{"award-number":["PG\/18\/43\/33688"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["RE\/18\/2\/34213"],"award-info":[{"award-number":["RE\/18\/2\/34213"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["CH\/1999001\/11735"],"award-info":[{"award-number":["CH\/1999001\/11735"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,22]]},"abstract":"<jats:p>\n                    Nox2 is a ROS-generating enzyme, deficiency of which increases suppression by Tregs in vitro and in an in vivo model of cardiac remodeling. As Tregs have emerged as a candidate therapy in autoimmunity and transplantation, we hypothesized that Nox2 deficiency in Tregs in recipient mice may improve outcomes in a heart transplant model. We generated a potentially novel B6129 mouse model with Treg-targeted Nox2 deletion (Nox2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    FoxP3Cre\n                    <jats:sup>+<\/jats:sup>\n                    mice) and transplanted with hearts from CB6F1 donors. As compared with those of littermate controls, Nox2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    FoxP3Cre\n                    <jats:sup>+<\/jats:sup>\n                    mice had lower plasma levels of alloantibodies and troponin-I, reduced levels of IFN-\u03b3 in heart allograft homogenates, and diminished cardiomyocyte necrosis and allograft fibrosis. Single-cell analyses of allografts revealed higher absolute numbers of Tregs and lower CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration in Nox2-deficient recipients compared with Nox2-replete mice. Mechanistically, in addition to a greater suppression of CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>\u2013<\/jats:sup>\n                    T effector cell proliferation and IFN-\u03b3 production, Nox2-deficient Tregs expressed higher levels of CCR4 and CCR8, driving cell migration to allografts; this was associated with increased expression of miR-214-3p. These data indicate that Nox2 deletion in Tregs enhances their suppressive ability and migration to heart allografts. Therefore, Nox2 inhibition in Tregs may be a useful approach to improve their therapeutic efficacy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.149301","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T12:03:06Z","timestamp":1628596986000},"source":"Crossref","is-referenced-by-count":12,"title":["Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-2458","authenticated-orcid":true,"given":"Silvia C.","family":"Trevelin","sequence":"first","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."},{"name":"King\u2019s College London, School of Immunology and Microbial Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7257-8624","authenticated-orcid":true,"given":"Anna","family":"Zampetaki","sequence":"additional","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2801-1900","authenticated-orcid":true,"given":"Greta","family":"Sawyer","sequence":"additional","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9844-6518","authenticated-orcid":true,"given":"Aleksandar","family":"Ivetic","sequence":"additional","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison C.","family":"Brewer","sequence":"additional","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley Ann","family":"Smyth","sequence":"additional","affiliation":[{"name":"University of East London, Health Sports Bioscience, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Marelli-Berg","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3370-5501","authenticated-orcid":true,"given":"Robert","family":"K\u00f6chl","sequence":"additional","affiliation":[{"name":"King\u2019s College London, School of Immunology and Microbial Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I.","family":"Lechler","sequence":"additional","affiliation":[{"name":"King\u2019s College London, School of Immunology and Microbial Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-0631","authenticated-orcid":true,"given":"Ajay M.","family":"Shah","sequence":"additional","affiliation":[{"name":"King\u2019s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Lombardi","sequence":"additional","affiliation":[{"name":"King\u2019s College London, School of Immunology and Microbial Sciences, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"issue":"3","key":"B1","first-page":"549","article-title":"Long-term outcome following heart transplantation: current perspective","volume":"7","author":"Wilhelm","year":"2015","journal-title":"J Thorac Dis"},{"issue":"10","key":"B2","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.86419","article-title":"Induced regulatory T cells in allograft tolerance via transient mixed chimerism","volume":"1","author":"Hotta","year":"2016","journal-title":"JCI Insight"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nri2785"},{"issue":"3","key":"B4","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). 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