title: Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program.
abstract: Allergic contact hypersensitivity (CHS) is an inflammatory skin disease mediated by allergen specific T cells. 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(+) and CD8(+) 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(-/-) 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(+)/CD8(+) T cell tolerance by regulating AICD process in the T cell mediated skin inflammation.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, Republic of Korea.
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Kwon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, Republic of Korea.|Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
authors.forename: Gi-Cheon
authors.initials: GC
authors.lastname: Kim
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.|New Drug Development center, Daegu Gyeongbuk Medical Innovation Foundation, 80, Cheombok-ro, Dong-gu, Daegu, Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Chonnam National University Medical School, Gwangju 501-749, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
authors.forename: Chang-Suk
authors.initials: CS
authors.lastname: Chae
authors.affiliation: Chonnam National University Medical School, Gwangju 501-749, Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Nam
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, Republic of Korea.
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
authors.forename: Dipayan
authors.initials: D
authors.lastname: Rudra
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.|Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.|Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors