{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:52:40Z","timestamp":1790751160559,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T00:00:00Z","timestamp":1407715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB900"],"award-info":[{"award-number":["SFB900"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>Foxp3 specifies the <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg cell lineage and is indispensable for immune tolerance. Accordingly, rare <jats:italic>Foxp3<\/jats:italic> mutations cause lethal autoimmunity. The mechanisms precipitating more prevalent human autoimmune diseases are poorly understood, but involve a combination of genetic and environmental factors. Many autoimmune diseases associate with a partial Treg\u2010cell dysfunction, yet mouse models reflecting such complex pathophysiological processes are rare. Around 95% of Foxp3<jats:sup>+<\/jats:sup> Treg cells can be specifically depleted in bacterial artifical chromosome (BAC)\u2010transgenic Depletion of REGulatory T\u00a0cells (DEREG) mice through diphtheria toxin (<jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content>) treatment. However, Treg\u2010cell depletion fails to cause autoimmunity in adult <jats:styled-content style=\"fixed-case\">DEREG<\/jats:styled-content> mice for unclear reasons. By crossing Foxp3<jats:sup>GFP<\/jats:sup> knock\u2010in mice to <jats:styled-content style=\"fixed-case\">DEREG<\/jats:styled-content> mice, we introduced additional genetic susceptibility that does not affect untreated mice. Strikingly, <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content> treatment of <jats:styled-content style=\"fixed-case\">DEREG<\/jats:styled-content> \u00d7 Foxp3<jats:sup>GFP<\/jats:sup> mice rapidly causes autoimmunity characterized by blepharitis, tissue damage, and autoantibody production. This inflammatory disease is associated with augmented T\u2010cell activation, increased Th2 cytokine production and myeloproliferation, and is caused by defective Treg\u2010cell homeostasis, preventing few <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content>\u2010insensitive Treg cells from repopulating the niche after Treg\u2010cell depletion. Our study provides important insights into self\u2010tolerance. We further highlight DEREG \u00d7 Foxp3<jats:sup>GFP<\/jats:sup> mice as a model to investigate the role of environmental factors in precipitating autoimmunity. This may help to better understand and treat human autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.201344315","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T19:56:49Z","timestamp":1405454209000},"page":"2990-3002","source":"Crossref","is-referenced-by-count":43,"title":["Few Foxp3<sup>+<\/sup> regulatory T\u00a0cells are sufficient to protect adult mice from lethal autoimmunity"],"prefix":"10.1002","volume":"44","author":[{"given":"Christian T.","family":"Mayer","sequence":"first","affiliation":[{"name":"Institute of Infection Immunology TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyman","family":"Ghorbani","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Research Center ImmunoScience Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Campus Benjamin Franklin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"St\u00fcve","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Hegemann","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Berod","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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