NFAT1 Regulates Systemic Autoimmunity through the Modulation of a Dendritic Cell Property

Title
NFAT1 Regulates Systemic Autoimmunity through the Modulation of a Dendritic Cell Property
Authors
이충구채창석김기천박은실Ravi Verma조학림전창덕유영준임신혁
Issue Date
2017-11
Publisher
The journal of immunology : official journal of the American Association of Immunologists
Citation
VOL 199, NO 9-3062
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-kappa B-mediated signaling pathways and enhanced binding of NF-kappa B (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-1 beta, IL-6, IL-12, and TNF-alpha, which preferentially induce Th1/Th17 cell differentiation. Our data suggest that NFAT1 may limit the hyperactivation of the NF-kappa B-mediated proinflammatory response in DCs and suppress autoimmunity by serving as a key regulator of DC tolerance.
URI
http://pubs.kist.re.kr/handle/201004/69609
ISSN
0022-1767
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE