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

Scientific Reports
Ho-Keun KwonSin-Hyeog Im

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 ce...Continue Reading

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Citations

Oct 4, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chang-Suk ChaeSin-Hyeog Im
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Noriko KitamuraOsamu Kaminuma
Apr 4, 2021·International Journal of Molecular Sciences·Noriko Kitamura, Osamu Kaminuma

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Methods Mentioned

BETA
PMA
flow cytometry
immunoprecipitation
nuclear translocation
PCR
FACS
transfection
ChIP

Software Mentioned

JASPAR
TRANSFAC
PROMO

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