The Human IL-3/Granulocyte-Macrophage Colony-Stimulating Factor Locus Is Epigenetically Silent in Immature Thymocytes and Is Progressively Activated during T Cell Development

Mirabella, Fabio; Baxter, Euan W.; Boissinot, Marjorie; James, Sally; Cockerill, Peter N.

doi:10.4049/jimmunol.0901364

Cited by 27 publications

(58 citation statements)

References 48 publications

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“…4). The HP0RP2 genes, that show a similar expression profile in Flu-TM and TIM, include two transcriptions factors Irf8 28 and Traf5 29 that control the optimal generation of effector CD8 T cells and two cytokines IL-3 and Xcl1 that have been previously shown to be poised in memory CD4 or CD8 T cells3031. The HP0RP3 highlights new poised genes such as Il1rl1 that codes for the receptor for the IL-33 alarmin that is produced by non hematopoietic cells during the course of viral infections and that plays an essential role in the development of anti-viral effector CD8 T cells32.…”

Section: Resultsmentioning

confidence: 99%

Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

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Section: Resultsmentioning

confidence: 99%

Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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“…(A) Naïve T cells are transformed by T cell receptor (TCR) signaling, leading to cytokine-dependent proliferation and differentiation, before reverting to quiescent memory T cells. (B,C) Quantitative PCR analyses of CSF2 mRNA expression relative to B2M mRNA expression in T cell subsets derived from CSF2 transgenic mice (23). Previously activated CD4 blast cells and memory T cells rapidly induce CSF2 mRNA when TCR signaling pathways are activated by PMA and calcium ionophore (B) (10).…”

Section: T Cell Activation and Differentiationmentioning

confidence: 99%

T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation

et al. 2017

Self Cite

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Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli. At the conclusion of this response, a small proportion of these cells return to the quiescent state as long-term memory T cells. We proposed that priming elements can be established in a hit-and-run process dependent on the inducible factor AP-1, but then maintained by the constitutive factors RUNX1 and ETS-1. This priming mechanism may also function to render genes receptive to additional differentiation-inducing factors such as GATA3 and TBX21 that are encountered under polarizing conditions. The proliferation of recently activated T cells and the maintenance of immunological memory in quiescent memory T cells are also dependent on various cytokine signaling pathways upstream of AP-1. We suggest that immunological memory is established by T cell receptor signaling, but maintained by cytokine signaling.

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“…These studies postulated that the pool of memory T cells would have been exposed to an antigen and retain the chromatin state of previous inductions but remains dormant until future antigenic encounters [57,89]. Several groups have proposed that this 'memory' of previous activation is encoded by the chromatin at the promoters of the more easily activated genes [108][109][110]. A ChIP-seq study of the H3K4me3 and H3K27me3 profiles in naive and memory CD8 + T cells revealed that a subset of the genes (e.g., Plagl1) that respond to a greater extent in memory cells have higher levels of H3K4me3 [109].…”

Section: Role Of Chromatin In Immune Cell Memorymentioning

confidence: 99%

Epigenetic Control of Inducible Gene Expression in the Immune System

Lim

Shannon

Hardy³

2010

Epigenomics

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It has been well documented that active genes, and their promoters and enhancers have a different chromatin or epigenomic environment compared with unexpressed genes. In addition, the epigenome may influence not only which genes are expressed, but also which genes can be induced in response to activation or differentiation signals. Immune cells respond to activation signals by rapidly inducing the expression of specific gene sets, and therefore this is a good system in which to examine the role of the epigenome in gene activation and cell differentiation. Several studies have now found that many immediate-early inducible genes exist in a similar epigenomic environment to active genes even in the unstimulated state. Some studies suggest that subsets of these genes may even have RNA polymerase II at their promoters and induction may be controlled downstream of its recruitment. Other inducible genes, however, undergo changes to histone modifications, levels or variant composition upon activation. In this article, we discuss how the epigenome of immune cells regulates inducible gene expression and discuss the differences between the immediate responses to activation signals and the longer term changes observed during differentiation.

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The Human IL-3/Granulocyte-Macrophage Colony-Stimulating Factor Locus Is Epigenetically Silent in Immature Thymocytes and Is Progressively Activated during T Cell Development

Cited by 27 publications

References 48 publications

Immune signatures of protective spleen memory CD8 T cells

Immune signatures of protective spleen memory CD8 T cells

T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation

Epigenetic Control of Inducible Gene Expression in the Immune System

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