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J Immunol. 2017 Nov 1;199(9):3051-3062. doi: 10.4049/jimmunol.1700882. Epub 2017 Sep 29.

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

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Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37673, Republic of Korea.
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea; and.
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37673, Republic of Korea;
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.


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-κB-mediated signaling pathways and enhanced binding of NF-κB (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-1β, IL-6, IL-12, and TNF-α, which preferentially induce Th1/Th17 cell differentiation. Our data suggest that NFAT1 may limit the hyperactivation of the NF-κB-mediated proinflammatory response in DCs and suppress autoimmunity by serving as a key regulator of DC tolerance.

[Indexed for MEDLINE]

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