Epigenetic Control of Immunity

Busslinger, Meinrad; Tarakhovsky, Alexander

doi:10.1101/cshperspect.a019307

Cited by 110 publications

(95 citation statements)

References 145 publications

(241 reference statements)

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“…Transcriptionally repressive heterochromatin is generated by several key complexes, including HDACs, the H3K27me3-associated polycomb repressive complex 1 (PRC1) and PRC2, and the H3K9me3-associated HMTs, and it seems to have a central role in preventing phenotypic plasticity between the polarized subsets 136,149 . In T Reg cells, HDAC3 interacts with FOXP3 to repress the expression of IL-2 and IL-17 (REF.…”

Section: Inhibiting Dna Accessibility With Heterochromatinmentioning

confidence: 99%

“…The pervasive dysregulation of chromatin regulation in cancer has led to the development of selective inhibi tors of many regulatory enzymes, notably EZH2, that may be repurposed to provide novel means to control T cell plasticity 149,152,153 . In cancer, such targeting strategies could have dual effects by directly impeding the cancer cells and by modulating the antitumour immune response 189 .…”

Section: Gene Expression Regulationmentioning

confidence: 99%

“…Alternatively, blocking the interactions of bromodomain-containing proteins with acetylated histones through the use of BET inhibitors (bromo domain and extraterminal inhibitors) reduces the severity of autoimmune disease in mouse models of multiple sclerosis and type 1 diabetes by broadly skewing immunity towards regulatory phenotypes 191,192 . Finally, the fact that pathogens express proteins that mimic histone modification sites, which modulate chromatin functions and allow for immune escape, provides strong evolutionary evidence that targeting specific chromatin modifiers can affect T cell function 149 .…”

Section: Gene Expression Regulationmentioning

confidence: 99%

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Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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| CD4 + T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4 + T cell plasticity by examining the molecular mechanisms that regulate it -from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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Section: Inhibiting Dna Accessibility With Heterochromatinmentioning

confidence: 99%

Section: Gene Expression Regulationmentioning

confidence: 99%

Section: Gene Expression Regulationmentioning

confidence: 99%

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Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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“…4 of Busslinger and Tarakhovsky 2014). Epigenetic information, on the other hand, is established in the gametes (Fig.…”

Section: The Genetic and Epigenetic Continuum Of The Mammalian Life Cmentioning

confidence: 99%

Germline and Pluripotent Stem Cells

Reik

Surani

2015

Cold Spring Harb Perspect Biol

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SUMMARYEpigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.

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“…DNA methylation patterns are copied and maintained by DNA methyltransferases (DNMTs) (Jeltsch, 2008) whereas DNA demethylation processes are achieved through more complex DNA excision/repair-based mechanisms (Barreto et al, 2007; Guo et al, 2011a;Morgan et al, 2004;Schmitz et al, 2009;Wu and Zhang, 2014). Together, these epigenetic mechanisms have been shown to be involved in the immune response to pathogens as well as in neuronal activity and also underlie the mechanism of learning (Busslinger and Tarakhovsky, 2014; Day et al, 2013; Garden, 2013;Guo et al, 2011b;Ma et al, 2009;Quintin et al, 2014;Russ et al, 2013). …”

mentioning

confidence: 99%

The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity

Provençal

Booij

Tremblay

2015

Journal of Experimental Biology

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Longitudinal epidemiological studies with birth cohorts have shown that physical aggression in humans does not appear suddenly in adolescence as commonly thought. In fact, physically aggressive behaviour is observed as early as 12 months after birth, its frequency peaks around 2-4 years of age and decreases in frequency until early adulthood. However, a minority of children (3-7%) maintain a high frequency of physical aggression from childhood to adolescence and develop serious social adjustment problems during adulthood. Genetic factors and early social experiences, as well as their interaction, have been shown to play an important role in the development of chronic aggressive behaviour. However, the biological mechanisms underlying these associations are just beginning to be uncovered. Recent evidence suggests that epigenetic mechanisms are responsive to adverse environments and could be involved in the development of chronic aggression. Using both gene candidate and genomic approaches, recent studies have identified epigenetic marks, such as DNA methylation alterations in genes involved in the stress response and the serotonin and immune systems to be partly responsible for the long-lasting effects of early adversity. Further longitudinal studies with biological, environmental and behavioural assessments from birth onwards are needed to elucidate the sequence of events that leads to these long-lasting epigenetic marks associated with early adversity and aggression.KEY WORDS: Aggression, Physical aggression, Epigenetic, DNA methylation, Early-life stress, Development, Immune system, Serotonin, HPA axis IntroductionPhysical aggression is a crucial component of human and animal behaviour. Our ancestors, as well as most animals, needed this skill in order to eat, to protect themselves and their family against predators, to compete for mating as well as to acquire resources and territory. However, in socially organized species, aggression needs to be self-controlled because aggression can be fatal to other members of the social group and can lead to social exclusion of the aggressor (Barker et al., 2008;Tremblay and Nagin, 2005). Even if the need to use physical aggression on a daily basis in our civilized *Author for correspondence (nadine_provencal@psych.mpg.de) society has become rare, acts of violence account for 1.43 million deaths worldwide annually and are, in most cases, due to individual acts of aggression.Exposure to adverse social environments, such as child maltreatment, maternal antisocial behaviour and family dysfunction has been shown to predict chronic physical aggression (CPA) (Campbell et al., 2010;Nagin and Tremblay, 2001;Tremblay et al., 2004). Genetic studies also suggest that the frequency of physical aggression is, in part, inherited (Dionne et al., 2003;Hicks et al., 2004;Lacourse et al., 2014). Moreover, genetic and environmental factors have been shown to interact in the expression of impulsive aggression in monkeys (Bennett et al., 2002) and violence in humans (Caspi et al., 200...

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Epigenetic Control of Immunity

Cited by 110 publications

References 145 publications

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

Germline and Pluripotent Stem Cells

The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity

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