Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells

Bandyopadhyay, Souvik; Duré, Myrianne; Paroder, Monika; Soto-Nieves, Noemí; Puga, Irene; Macián, Fernando

doi:10.1182/blood-2006-07-037754

Cited by 86 publications

(146 citation statements)

References 50 publications

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“…Previous studies have identified several genes that are upregulated in anergic CD4 + T cells when there is NFAT but not AP-1 transcriptional activation (20)(21)(22)(23)(24)(25)(26)(27). We therefore determined whether Sirt1, as a HDAC, induces and/or maintains CD4 + T cell tolerance by altering the expression of these anergic genes.…”

Section: Sirt1 Suppresses T Cell-dependent Immunity In Micementioning

confidence: 97%

The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice

Zhang¹,

Lee²,

Shannon³

et al. 2009

J. Clin. Invest.

263

286

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Although many self-reactive T cells are eliminated by negative selection in the thymus, some of these cells escape into the periphery, where they must be controlled by additional mechanisms. However, the molecular mechanisms underlying peripheral T cell tolerance and its maintenance remain largely undefined. In this study, we report that sirtuin 1 (Sirt1), a type III histone deacetylase, negatively regulates T cell activation and plays a major role in clonal T cell anergy in mice. In vivo, we found that loss of Sirt1 function resulted in abnormally increased T cell activation and a breakdown of CD4 + T cell tolerance. Conversely, upregulation of Sirt1 expression led to T cell anergy, in which the activity of the transcription factor AP-1 was substantially diminished. Furthermore, Sirt1 interacted with and deacetylated c-Jun, yielding an inactive AP-1 factor. In addition, Sirt1-deficient mice were unable to maintain T cell tolerance and developed severe experimental allergic encephalomyelitis as well as spontaneous autoimmunity. These findings provide insight into the molecular mechanisms of T cell activation and anergy, and we suggest that activators of Sirt1 may be useful as therapeutic agents for the treatment and/or prevention of autoimmune diseases.

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Section: Sirt1 Suppresses T Cell-dependent Immunity In Micementioning

confidence: 97%

The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice

Zhang¹,

Lee²,

Shannon³

et al. 2009

J. Clin. Invest.

263

286

View full text Add to dashboard Cite

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“…Anergy-associated genes are different from those genes activated during a productive immune response, and therefore their expression must be regulated by different transcriptional complexes (9,26,27). These genes include, among others, several E3 ubiquitin ligases, such as Cblb, Itch, and Grail; transcription factors, such as Egr2, Egr3, and Ikaros; Caspase3; and diacylglycerol kinase  (Dgka) (9,(28)(29)(30)(31)(32)(33)(34)(35). The expression of many of these genes seems to be controlled by NFAT, as their expression is drastically reduced in T cells that lack NFAT1 (9).…”

mentioning

confidence: 99%

Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance

Soto-Nieves¹,

Puga²,

Abe³

et al. 2009

J Cell Biol

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“…Aiolos is a transcription factor of the Ikaros family involved in the development of lymphoid cell lineages (5,29,46) through different mechanisms, for example the regulation of the epigenetic status of target genes (47)(48)(49). In human Treg cells, for instance, FoxP3 and Aiolos form a heterodimeric complex that binds the Il2 promoter and suppresses IL-2 expression (29).…”

Section: Ahr-dependent Immune Cell Regulationmentioning

confidence: 99%

Control of immune-mediated pathology via the aryl hydrocarbon receptor

Wheeler

Rothhammer

Quintana

2017

Journal of Biological Chemistry

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Edited by George M. Carman Genetic and environmental factors contribute to the development of immune-mediated diseases. Although numerous genetic factors contributing to autoimmunity have been identified in recent years, our knowledge on environmental factors contributing to the pathogenesis of autoimmune diseases and the mechanisms involved is still limited. In this context, the diet, microbiome, geographical location, as well as environmental pollutants have been shown to modulate autoimmune disease development. These environmental factors interact with cellular components of the immune system in distinct and defined ways and can influence immune responses at the transcriptional and protein level. Moreover, endogenous metabolites generated from basic cellular processes such as glycolysis and oxidative phosphorylation also contribute to the shaping of the immune response. In this minireview, we highlight recent progress in our understanding of the modulation of the immune response by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor whose activity is regulated by small molecules provided by diet, commensal flora, environmental pollutants, and metabolism. We focus on the role of AhR in integrating signals from the diet and the intestinal flora to modulate ongoing inflammation in the central nervous system, and we also discuss the potential therapeutic value of AhR agonists for multiple sclerosis and other autoimmune diseases. Multiple sclerosis (MS)4 is an autoimmune disease of the central nervous system (CNS). In 85% of the affected individuals, MS initially presents with a relapsing-remitting course characterized by temporally defined relapses, which are followed by a varying degree of remission. Most patients eventually enter the secondary progressive phase of MS, which is characterized by the progressive and irreversible accumulation of neurological deficits (1). Several biological pathways are involved in the regulation of the immune response in MS both in the peripheral and central immune compartment and are thought to play dominant roles in the different stages of the disease. Although the role of several molecules such as cytokines and toll-like receptor agonists in MS pathology has been studied at length, particularly in relation to the relapsing-remitting phase of the disease, only recently has the role of metabolites generated in basic biological processes such as glycolysis and oxidative phosphorylation become appreciated with regard to their relevance for the development, propagation, and resolution of autoimmune inflammation. Prominent examples of endogenous metabolites with central roles in MS pathology include bioactive lipids, reactive oxygen species, and adenosine triphosphate (ATP) (2-13). The effects of these endogenous metabolites are modulated by a multitude of exogenous factors such as pollutants, dietary factors, and products from the commensal flora to trigger transcriptional programs that control the immune response during MS. Ultimately, the understanding of ...

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Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells

Cited by 86 publications

References 50 publications

The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice

The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice

Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance

Control of immune-mediated pathology via the aryl hydrocarbon receptor

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