TGF-β and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3

Samanta, Arabinda; Li, Bin; Song, Xiaomin; Bembas, Kathryn; Zhang, Geng; Katsumata, Makoto; Saouaf, Sandra J.; Wang, Qiang; Hancock, Wayne W.; Shen, Yuan; Greene, Mark I.

doi:10.1073/pnas.0806726105

Cited by 141 publications

(125 citation statements)

References 44 publications

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“…For example, deacetylation of Foxp3 protein has been linked to impaired function of Treg cells by affecting Foxp3 protein stability and its ability to bind to gene promoters. TGF-␤ signaling was identified to modulate the deacetylation of Foxp3, and TIP60, p300, and sirtuin-1 were subsequently shown to regulate Foxp3 acetylation (38,39). It is well known that a substrate molecule with different phosphorylation sites may occupy multipotential states.…”

Section: Discussionmentioning

confidence: 99%

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Wang¹,

Zhang²,

Wang

et al. 2016

Journal of Biological Chemistry

115

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Section: Discussionmentioning

confidence: 99%

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Wang¹,

Zhang²,

Wang

et al. 2016

Journal of Biological Chemistry

115

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“…However, we did not immediately anticipate that IL-6 would also contribute to the significant increase in IFN-g production by the T cells. One possible explanation may lie in the fact that IL-6 is known to inhibit Foxp3 (32,33), the transcription factor associated with Tregs, which inhibit the activation of other T cell subsets. Therefore, the presence of IL-6 in T cell-fibroblast cocultures might reduce the number or function of Tregs and thus increase the activation potential and cytokine production of the rest of the T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors

Barnas

Simpson-Abelson

Brooks

et al. 2010

The Journal of Immunology

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Fibroblasts are a dominant cell type in most human solid tumors. The possibility that fibroblasts have the capacity to interact with and modulate the function of tumor-associated T lymphocytes makes them a potential therapeutic target. To address this question, primary cultures of fibroblasts derived from human lung tumors were established and cultured with T cells derived from the same tumor. The tumor fibroblasts significantly enhance the production of IFN-γ and IL-17A by the tumor-associated T cells following a CD3/CD28-induced activation of the T cells. This enhancement was fibroblast cell dose-dependent and did not require direct contact between the two cell types. Tumor-associated fibroblast-conditioned media similarly enhanced both IFN-γ and IL-17A in activated T cells, and this enhancement was significantly reduced by Abs to IL-6. Conditioned media derived from activated lymphocyte cultures significantly enhanced IL-6 production by tumor fibroblasts. A similar enhancement of IFN-γ and IL-17A was observed when activated T cells from a normal donor were cultivated with skin fibroblasts derived from the same donor. These results establish that fibroblasts and autologous lymphocytes, whether derived from the tumor microenvironment or from nonmalignant tissues, have the capacity to reciprocally interact and modulate function. In contrast to other reports, fibroblasts are shown to have an immunostimulatory effect upon activated T lymphocytes. The ability of fibroblasts to enhance two T cell cytokines known to have an impact upon tumor progression suggests that fibroblasts play an important role in tumor pathogenesis that could be exploited therapeutically.

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“…FOXP3 is also likely to modulate gene expression through epigenetic mechanisms, such as chromatin remodeling and histone deacetylation (25,26). It is evident that the composition and activity of the FOXP3 regulatory complex is dynamic and is influenced by external stimuli acting partly through the posttranslational modification of FOXP3 (27,28). These observations demonstrate the complex nature of the interaction of FOXP3 with its target genes.…”

mentioning

confidence: 88%

Genome-Wide Identification of Human FOXP3 Target Genes in Natural Regulatory T Cells

Sadlon

Wilkinson

Pederson

et al. 2010

The Journal of Immunology

128

162

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TGF-β and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3

Cited by 141 publications

References 44 publications

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors

Genome-Wide Identification of Human FOXP3 Target Genes in Natural Regulatory T Cells

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