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NFAT1 regulates systemic autoimmunity through the modulation of a dendritic cell property

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Title
NFAT1 regulates systemic autoimmunity through the modulation of a dendritic cell property
Author(s)
Chang-Suk Chae; Gi-Cheon Kim; Eun Sil Park; Choong-Gu Lee; Ravi Verma; Hagg-Lim Cho; Chang-Duk Jun; Yung Joon Yoo; Sin-Hyeog Im
Publication Date
2017-11
Journal
JOURNAL OF IMMUNOLOGY, v.199, no.9, pp.3051 - 3062
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
The transcription factor NFAT1 plays a pivotal role in the homeostasis of T lymphocytes. However, its functional importance in non-CD4+ T cells, especially in systemic immune disorders, is largely unknown. In this study, we report that NFAT1 regulates dendritic cell (DC) tolerance and suppresses systemic autoimmunity using the experimental autoimmune myasthenia gravis (EAMG) as a model. Myasthenia gravis and EAMG are T cell-dependent, Ab-mediated autoimmune disorders in which the acetylcholine receptor is the major autoantigen. NFAT1-knockout mice showed higher susceptibility to EAMG development with enhanced Th1/Th17 cell responses. NFAT1 deficiency led to a phenotypic alteration of DCs that show hyperactivation of NF-kB-mediated signaling pathways and enhanced binding of NF-kB (p50) to the promoters of IL-6 and IL-12. As a result, NFAT1-knockout DCs produced much higher levels of proinflammatory cytokines such as IL-1b, IL-6, IL-12, and TNF-a, which preferentially induce Th1/Th17 cell differentiation. Our data suggest that NFAT1 may limit the hyperactivation of the NF-kB-mediated proinflammatory response in DCs and suppress autoimmunity by serving as a key regulator of DC tolerance. Copyright © 2017 by The American Association of Immunologists, Inc.
URI
https://pr.ibs.re.kr/handle/8788114/4158
ISSN
0022-1767
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
Files in This Item:
(2017_CS_Chae)NFAT1 Regulates Systemic Autoimmunity through the Modulation of a Dendritic Cell Property.pdfDownload

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