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In this study, we investigated the role of transcription factor NFAT1 in the pathogenesis of contact hypersensitivity. NFAT1 knock out (KO) mice spontaneously developed CHS-like skin inflammation in old age. Healthy young NFAT1 KO mice displayed enhanced susceptibility to hapten-induced CHS. Both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells from NFAT1 KO mice displayed hyper-activated properties and produced significantly enhanced levels of inflammatory T helper 1(Th1)\/Th17 type cytokines. NFAT1 KO T cells were more resistant to activation induced cell death (AICD) and regulatory T cells derived from these mice showed a partial defect in their suppressor activity. NFAT1 KO T cells displayed a reduced expression of apoptosis associated BCL-2\/BH3 family members. Ectopic expression of NFAT1 restored the AICD defect in NFAT1 KO T cells and increased AICD in normal T cells. Recipient Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>mice transferred with NFAT1 KO T cells showed more severe CHS sensitivity due to a defect in activation induced hapten-reactive T cell apoptosis. Collectively, our results suggest the NFAT1 plays a pivotal role as a genetic switch in CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup>T cell tolerance by regulating AICD process in the T cell mediated skin inflammation.<\/jats:p>","DOI":"10.1038\/srep19453","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T12:03:40Z","timestamp":1453118620000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program"],"prefix":"10.1038","volume":"6","author":[{"given":"Ho-Keun","family":"Kwon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi-Cheon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Sun","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Suk","family":"Chae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Hee","family":"Nam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Duk","family":"Jun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipayan","family":"Rudra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles D.","family":"Surh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sin-Hyeog","family":"Im","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,18]]},"reference":[{"key":"BFsrep19453_CR1","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1097\/ACI.0b013e3282ef6923","volume":"7","author":"A Cavani","year":"2007","unstructured":"Cavani, A., De Pita, O. & Girolomoni, G. 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