Histone/protein Deacetylase Inhibitors Increase Suppressive Functions of Human FOXP3+ Tregs

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2010 May 19

PMID 20478744

Citations 65

Authors

Tatiana Akimova

Guanghui Ge

Tatiana Golovina

Tatiana Mikheeva

Liqing Wang

James L Riley

Wayne W Hancock

Affiliations

Soon will be listed here.

Abstract

Histone/protein deacetylases (HDACs) decrease histone and protein acetylation, typically leading to suppression of gene transcription and modulation of various protein functions. We found significant differences in expression of HDAC before and after stimulation of human T regulatory (Treg) and T effector cells, suggesting the potential for future selective targeting of Tregs with HDAC inhibitors (HDACi). Use of various HDACi small molecules enhanced, by up to 4.5-fold (average 2-fold), the suppressive functions of both freshly isolated and expanded human Tregs, consistent with our previous murine data. HDACi use increased Treg expression of CTLA-4, a key negative regulator of immune response, and we found a direct and significant correlation between CTLA-4 expression and Treg suppression. Hence, HDACi compounds are promising pharmacologic tools to increase Treg suppressive functions, and this action may potentially be of use in patients with autoimmunity or post-transplantation.

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