Rules of Regulation

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Science  26 Oct 2007:
Vol. 318, Issue 5850, pp. 537
DOI: 10.1126/science.318.5850.537b

What overarching factors regulate the regulatory T (Treg) cells that guide our immune systems to fight infectious diseases while leaving ourselves unharmed? By scrutinizing molecular events inside Treg cells, Tao et al. implicate the activity of chromatin remodeling proteins. Initial evidence emerged from the observation that a histone deacetylase (HDAC) inhibitor increased the level of the chief transcription factor in Treg cells, Foxp3, as well as the number and activity of Treg cells in mice. Furthermore, in culture-stimulated Treg cells, HDAC9 was the most prominently expressed member of the deacetylase family, and Treg cell function was enhanced in its absence. Acetylation of the Foxp3 protein itself was also observed and corresponded with an increase in Foxp3 binding to its target genes. Finally, HDAC inhibition helped curtail inflammatory T cell responses, both to transplanted grafts and in a model of inflammatory bowel disease. The finding that regulating acetylation/deacetylation has such a measurable influence on Treg function and that it operates at the level of both the Foxp3 locus and the transcription factor suggests that different avenues might be open for testing HDAC inhibition as a form of immunotherapy. — SJS

Nat. Med. 13, 10.1038/nm1652 (2007).

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