Thymic Stromal‐Cell Abnormalities and Dysregulated T‐Cell Development in IL‐2‐Deficient Mice

Reya, Tannishtha; Bassiri, Hamid; Biancaniello, Renée; Carding, Simon R.

doi:10.1155/1998/19567

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…As a second example of Bptf-dependent changes in DNase I hypersensitivity, we examined Il2, which is not important for thymocyte maturation (Reya et al 1998) but whose chromatin structure is known to undergo specific changes during the commitment to the thymocyte lineage (Siebenlist et al 1986;Yui et al 2001). In DP thymocytes, we observed three DNase I-hypersensitive sites in Bptf KO DP thymocytes (Fig.…”

Section: Effects Of Bptf On Chromatin Structure Prior To Positive Selmentioning

confidence: 93%

Chromatin remodeling complex NURF regulates thymocyte maturation

Landry

Banerjee²,

Taylor³

et al. 2011

Genes Dev.

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The maturation of T cells requires signaling from both cytokine and T-cell receptors to gene targets in chromatin, but how chromatin architecture influences this process is largely unknown. Here we show that thymocyte maturation post-positive selection is dependent on the nucleosome remodeling factor (NURF). Depletion of Bptf (bromodomain PHD finger transcription factor), the largest NURF subunit, in conditional mouse mutants results in developmental arrest beyond the CD4 + CD8 int stage without affecting cellular proliferation, cellular apoptosis, or coreceptor gene expression. In the Bptf mutant, specific subsets of genes important for thymocyte development show aberrant expression. We also observed defects in DNase I-hypersensitive chromatin structures at Egr1, a prototypical Bptf-dependent gene that is required for efficient thymocyte development. Moreover, chromatin binding of the sequence-specific factor Srf (serum response factor) to Egr1 regulatory sites is dependent on Bptf function. Physical interactions between NURF and Srf suggest a model in which Srf recruits NURF to facilitate transcription factor binding at Bptf-dependent genes. These findings provide evidence for causal connections between NURF, transcription factor occupancy, and gene regulation during thymocyte development.

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Section: Effects Of Bptf On Chromatin Structure Prior To Positive Selmentioning

confidence: 93%

Chromatin remodeling complex NURF regulates thymocyte maturation

Landry

Banerjee²,

Taylor³

et al. 2011

Genes Dev.

View full text Add to dashboard Cite

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“…High levels of IL-2 are produced when T cells are activated through both the Ag-specific TCR interacting with peptide:MHC complexes on APCs and costimulatory interactions such as B7 on APCs with CD28 receptors on T cells (3). IL-2 is necessary for the generation of correct immune responses, as indicated by the fact that IL-2-deficient mice develop a thymic disorder that disrupts thymocyte development (4). Other conditions such as hemolytic anemia, chronic inflammatory bowel disease, and severe autoimmunity are also prevalent in IL-2-deficient mice leading to the conclusion that IL-2 plays a critical role in T cell homeostasis (5).…”

Section: T He Generation Of T Cell-mediated Immune Responses Ismentioning

confidence: 99%

“…The regulatory regions of the human IL-2 promoter have been studied in detail and it was initially established that ϳ300 nt upstream from the start of transcription was sufficient for maximal activity in transient transfection assays in Jurkat T cells (9,10). Within this minimal promoter region, two major TCR responsive regions were identified in the human gene and termed Ag-responsive elements (ARRE), 4 ARRE-1 and ARRE-2 (Ref. 11; see Fig.…”

Section: T He Generation Of T Cell-mediated Immune Responses Ismentioning

confidence: 99%

The Human IL-2 Gene Promoter Can Assemble a Positioned Nucleosome That Becomes Remodeled Upon T Cell Activation

Attema

Reeves

Murray

et al. 2002

The Journal of Immunology

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Controlled production of the cytokine IL-2 plays a key role in the mammalian immune system. Expression from the gene is tightly regulated with no detectable expression in resting T cells and a strong induction following T cell activation. The IL-2 proximal promoter (+1 to −300) contains many well-defined transcriptional activation elements that respond to T cell stimulation. To determine the role of chromatin structure in the regulation of interleukin-2 gene transcription, nucleosome assembly across the IL-2 promoter region was examined using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a nucleosome that is both translationally and rotationally positioned, spanning some of the major functional control elements. The binding of transcription factors to these elements, with the exception of the architectural protein HMGA1, was occluded by the presence of the nucleosome. Analysis of the chromatin architecture of the IL-2 gene in Jurkat T cells provided evidence for the presence of a similarly positioned nucleosome in vivo. The region encompassed by this nucleosome becomes remodeled following activation of Jurkat T cells. These observations suggest that the presence of a positioned nucleosome across the IL-2 proximal promoter may play an important role in maintaining an inactive gene in resting T cells and that remodeling of this nucleosome is important for gene activation.

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“…Tregs have been shown to constitutively express IL-2R (CD25), allowing Tregs to respond to low levels of IL-2 produced by conventional CD4+ T cells [10,11]. The removal of IL-2 from activated T cells can lead to a deprivation of cells, which is indicated by studies on IL2 -deficient mice [13]. The IL-2 receptor has three chains, α, β and γ, which constitute the high affinity IL2 receptor.…”

Section: Introductionmentioning

confidence: 99%

In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

et al. 2012

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BackgroundThe selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism.MethodsWe identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections.ResultsWe identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function.ConclusionsThe identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

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Thymic Stromal‐Cell Abnormalities and Dysregulated T‐Cell Development in IL‐2‐Deficient Mice

Cited by 16 publications

References 30 publications

Chromatin remodeling complex NURF regulates thymocyte maturation

Chromatin remodeling complex NURF regulates thymocyte maturation

The Human IL-2 Gene Promoter Can Assemble a Positioned Nucleosome That Becomes Remodeled Upon T Cell Activation

In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

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