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Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program

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Title
Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program
Author(s)
HK Kwon; Gi-Cheon Kim; Ji Sun Hwang; Y Kim; Chang-Suk Chae; JH Nam; CD Jun; Dipayan Rudra; Charles D. Surh; Sin-Hyeog Im
Publication Date
2016-01
Journal
SCIENTIFIC REPORTS, v.6, pp.19453
Publisher
NATURE PUBLISHING GROUP
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. Copyright © 2016, Macmillan Publishers Limited This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI
https://pr.ibs.re.kr/handle/8788114/2372
DOI
10.1038/srep19453
ISSN
2045-2322
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
(2016_GC_Kim)Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program.pdfDownload

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