The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation
Open accessAbstract
Foxp3, a winged-helix family transcription factor, serves as the master switch for CD4+ regulatory T cells (Treg). We identified a unique and evolutionarily conserved CpG-rich island of the Foxp3 nonintronic upstream enhancer and discovered that a specific site within it was unmethylated in natural Treg (nTreg) but heavily methylated in naive CD4+ T cells, activated CD4+ T cells, and peripheral TGFβ-induced Treg in which it was bound by DNMT1, DNMT3b, MeCP2, and MBD2. Demethylation of this CpG site using the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (Aza) induced acetylation of histone 3, interaction with TIEG1 and Sp1, and resulted in strong and stable induction of Foxp3. Conversely, IL-6 resulted in methylation of this site and repression of Foxp3 expression. Aza plus TGFβ-induced Treg resembled nTreg, expressing similar receptors, cytokines, and stable suppressive activity. Strong Foxp3 expression and suppressor activity could be induced in a variety of T cells, including human CD4+CD25− T cells. Epigenetic regulation of Foxp3 can be predictably controlled with DNMT inhibitors to generate functional, stable, and specific Treg.
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Cites
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
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Epigenetics in human disease and prospects for epigenetic therapy
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Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3
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Oxygen sensing by HIF hydroxylases
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Epigenetic Control of the foxp3 Locus in Regulatory T Cells
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Cited by
Zhou, X., Bailey-Bucktrout, S. L., Jeker, L. T., Penaranda, C., Martínez-Llordella, M., Ashby, M., Nakayama, M., Rosenthal, W., & Bluestone, J. A. (2009) · Nature Immunology · doi:10.1038/ni.1774 · Cited by 1,370
Epigenetic mechanisms that underpin metabolic and cardiovascular diseases
Gluckman, P. D., Hanson, M. A., Buklijas, T., Low, F. M., & Beedle, A. S. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.102 · Cited by 627
The regulation of immune tolerance by FOXP3
Lu, L., Barbi, J., & Pan, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.75 · Cited by 580
Control of the Inheritance of Regulatory T Cell Identity by a cis Element in the Foxp3 Locus
Feng, Y., Arvey, A., Chinen, T., van der Veeken, J., Gasteiger, G., & Rudensky, A. Y. (2014) · Cell · doi:10.1016/j.cell.2014.07.031 · Cited by 422
Pathophysiology of allergic inflammation
Barnes, P. J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01020.x · Cited by 361
Metadata
- Authors
- Lal, G., Zhang, N., van der Touw, W., Ding, Y., Ju, W., Bottinger, E. P., Reid, S. P., Levy, D. E., & Bromberg, J. S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-01
- Volume
- 182
- Issue
- 1
- Pages
- 259-273
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1674079630
- Cited by
- 559
- References
- 56
- FWCI
- 17.18
- Type
- journal article
- Language
- en
- Open access
- green
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- Lal, G., Zhang, N., van der Touw, W., Ding, Y., Ju, W., Bottinger, E. P., Reid, S. P., Levy, D. E., & Bromberg, J. S. (2009). Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation. The Journal of Immunology. https://doi.org/10.4049/jimmunol.182.1.259
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