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In models of acute (dextran sodium sulfate and trinitrobenzene sulfonic acid) and chronic (dextran sodium sulfate) toxic colitis, therapeutic doses of the fusion proteins improved survival and prevented colon shortening. While both chimeric proteins eradicated CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> T cells in mesenteric LN, IL2\u2010DT caused severe lymphopenia. In contrast, IL2\u2010cas was equally protective and increased fractional expression of Foxp3. Similar effects of the fusion proteins were observed in healthy mice: IL2\u2010DT caused lymphopenia and IL2\u2010cas increased fractional expression of FoxP3. The fusion proteins induced apoptosis in CD25<jats:sup>+<\/jats:sup> T cells <jats:italic>in vitro<\/jats:italic>, with lower toxicity of IL2\u2010cas to Foxp3<jats:sup>+<\/jats:sup> T cells. These data infer that targeted depletion of cells expressing the IL\u20102 receptor has therapeutic potential in models of inflammatory colitis, despite depletion of CD25<jats:sup>+<\/jats:sup> Treg. The IL2\u2010cas fusion protein is particularly relevant to inflammatory bowel disease, as direct internalization of toxic moieties overcomes multiple pathways of resistance to apoptosis of colitogenic T cells.<\/jats:p>","DOI":"10.1002\/eji.200839190","type":"journal-article","created":{"date-parts":[[2009,9,4]],"date-time":"2009-09-04T09:46:53Z","timestamp":1252057613000},"page":"2850-2864","source":"Crossref","is-referenced-by-count":11,"title":["Targeted therapy to the IL\u20102R using diphtheria toxin and caspase\u20103 fusion proteins modulates Treg and ameliorates inflammatory colitis"],"prefix":"10.1002","volume":"39","author":[{"given":"Shai","family":"Yarkoni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuval","family":"Sagiv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayelet","family":"Kaminitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel L.","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadir","family":"Askenasy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,10,2]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"417","article-title":"Changes in colonic mucosal permeability mouse 1. 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