Histone Deacetylase Sirtuin 1 Deacetylates IRF1 Protein and Programs Dendritic Cells to Control Th17 Protein Differentiation during Autoimmune Inflammation

Yang, Hee‐Young; Lee, Sang Myeong; Gao, Beixue; Zhang, Jinping; Fang, Deyu

doi:10.1074/jbc.m113.527531

Cited by 65 publications

(58 citation statements)

References 48 publications

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“…The lack of SIRT1 in DCs reduced critical cytokine production, including IFNβ and IL-12, which we suggest contributed to a pathological Th2/Th17 immune response within the airways. Previous studies examining DC-specific KO mice reported no changes in DC maturation, differentiation, or development compared to WT DCs (39, 40), in agreement with our observations. Thus, our data indicate that SIRT1 has a unique role in modulating DC cytokine production in the context of a viral infection, such as RSV (12).…”

Section: Discussionsupporting

confidence: 93%

Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Owczarczyk

Schaller

Reed

et al. 2015

The Journal of Immunology

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Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in children worldwide. Sirtuin 1 (SIRT1), an NAD+ dependent deacetylase, has been associated with the induction of autophagy and the regulation of inflammatory mediators. We found that Sirt1 was upregulated in mouse lung after RSV infection. Infected animals that received EX-527, a selective SIRT1 inhibitor, displayed exacerbated lung pathology, with increased mucus production, elevated viral load, and enhanced Th2 cytokine production. Gene expression analysis of isolated cell populations revealed that Sirt1 was most highly upregulated in RSV-treated dendritic cells (DCs). Upon RSV infection, EX-527-treated DCs, Sirt1 siRNA-treated DCs, or DCs from conditional knockout (Sirt1f/f-CD11c–Cre+) mice showed downregulated inflammatory cytokine gene expression and attenuated autophagy. Finally, RSV infection of Sirt1f/f-CD11c–Cre+ mice resulted in altered lung and lymph node cytokine responses, leading to exacerbated pathology. These data indicate that SIRT1 promotes DC activation associated with autophagy-mediated processes during RSV infection, thereby directing efficient antiviral immune responses.

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Section: Discussionsupporting

confidence: 93%

Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Owczarczyk

Schaller

Reed

et al. 2015

The Journal of Immunology

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“…In muscle cells, activation of the AMP/ATP sensor AMP kinase (AMPK) results in increased NAD + /NADH ratios and sirtuin 1 (SIRT1) activation 116 , resulting in deacetylation of PGC1α and promotion of metabolic pathways that restore NAD + /NADH ratios. In dendritic cells (DCs), SIRT1 mediates the deacetylation of interferon (IFN)-regulatory factor 1 (IRF1) and, in doing so, inhibits the ability of cells to produce interleukin-27 (IL-27) and IFNβ 117 . SIRT1 has also been reported to regulate the balance of IL-12p70 versus IL-23 production 118 and to repress PPARγ activity in DCs 119 .…”

Section: Signalling By Intracellular Metabolites In Dcsmentioning

confidence: 99%

Dendritic cell metabolism

2014

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The past 15 years have seen enormous advances in our understanding of the receptor and signalling systems that allow dendritic cells (DCs) to respond to pathogens or other danger signals and initiate innate and adaptive immune responses. We are now beginning to appreciate that many of these pathways not only stimulate changes in the expression of genes that control DC immune functions, but also affect metabolic pathways, thereby integrating the cellular requirements of the activation process. In this Review, we focus on this relatively new area of research and attempt to describe an integrated view of DC immunometabolism.

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“…Genetic polymorphisms of histone-modifying genes can also cause dysfunction of these genes and aberrant histone modifications (114–116), which may further results in AITD. Sirtuin1 (SIRT1) is a class 3 nicotinamide adenine dinucleotide-dependent HDAC, which is intensively associated with immune response and autoimmune diseases (114–116).…”

Section: Epigenetics In Aitdmentioning

confidence: 99%

“…Sirtuin1 (SIRT1) is a class 3 nicotinamide adenine dinucleotide-dependent HDAC, which is intensively associated with immune response and autoimmune diseases (114–116). A case–control study by Sarumaru et al reported that rs3758391 and rs4746720 in the SIRT1 gene were associated with higher levels of thyroid autoantibodies in AITD patients (117).…”

Section: Epigenetics In Aitdmentioning

confidence: 99%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

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Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell-mediated organ-specific autoimmune diseases. Graves’ disease and Hashimoto thyroiditis are the two main clinical presentations of AITD. Both genetic and environmental factors have important roles in the development of AITD. Epigenetics have been considered to exert key roles in integrating those genetic and environmental factors, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD. Recent studies on the epigenetics of AITD have provided some novel insights into the pathogenesis of AITD. The aim of this review is to provide an overview of recent advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone modifications, and non-coding RNAs. This review highlights the key roles of epigenetics in the pathogenesis of AITD and potential clinical utility. However, the epigenetic roles in AITD are still not fully elucidated, and more researches are needed to provide further deeper insights into the roles of epigenetics in AITD and to uncover new therapeutic targets. Although there are many studies assessing the epigenetic modifications in AITD patients, the clinical utility of epigenetics in AITD remains poorly defined. More studies are needed to identify the underlying epigenetic modifications that can contribute to accurate diagnosis of AITD, adequate choice of treatment approach, and precise prediction of treatment outcomes.

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Histone Deacetylase Sirtuin 1 Deacetylates IRF1 Protein and Programs Dendritic Cells to Control Th17 Protein Differentiation during Autoimmune Inflammation

Cited by 65 publications

References 48 publications

Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus–Induced Immune Responses

Dendritic cell metabolism

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

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