Research ArticleImmunology

Histone Deacetylases 6 and 9 and Sirtuin-1 Control Foxp3+ Regulatory T Cell Function Through Shared and Isoform-Specific Mechanisms

Sci. Signal.  19 Jun 2012:
Vol. 5, Issue 229, pp. ra45
DOI: 10.1126/scisignal.2002873

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Enhancing Regulatory T Cell Function

Some therapies designed to help patients suffering from autoimmune diseases or recovering from organ transplant involve the removal of the patient’s regulatory T cells (Tregs), which suppress the undesirable proinflammatory actions of effector T cells, so that they can be expanded in number ex vivo before being put back into the patient. One problem associated with this approach is that the phenotype of the administered Tregs is unstable, and so their suppressive function is lost over time. Previous studies have shown that inhibition of certain members of the family of histone deacetylases (HDACs) enhances the function of Tregs. Through experiments with mice deficient in distinct HDACs and treated with HDAC-specific inhibitors, Beier et al. have demonstrated the mechanisms by which the simultaneous inhibition of combinations of distinct HDACs improved the suppressive function of Tregs and enhanced their stability, which suggests that such an approach may be of benefit to patients reliant on such therapies.