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Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs

Tatiana Akimova1, Guanghui Ge, Tatiana Golovina

  • 1Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104-4318, USA.

Clinical Immunology (Orlando, Fla.)
|May 19, 2010
PubMed

Insights

Histone deacetylase inhibitors (HDACi) enhance the function of T regulatory cells (Tregs). This suggests HDACi could be used to treat autoimmune diseases and in post-transplantation care.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Histone/protein deacetylases (HDACs) regulate gene transcription and protein function by decreasing acetylation.
  • T regulatory (Treg) and T effector cells show differential HDAC expression upon stimulation.
  • HDAC inhibitors (HDACi) represent a potential therapeutic strategy for modulating immune responses.

Purpose of the Study:

  • To investigate the effect of HDAC inhibitors on human T regulatory cell function.
  • To explore the correlation between HDAC inhibition, CTLA-4 expression, and Treg suppressive activity.

Main Methods:

  • Analysis of HDAC expression in human Treg and T effector cells before and after stimulation.
  • Treatment of human Tregs with various small molecule HDAC inhibitors.
  • Quantification of Treg suppressive function and CTLA-4 expression.

Main Results:

  • HDACi significantly enhanced the suppressive functions of human Tregs (up to 4.5-fold).
  • HDACi treatment increased Treg expression of CTLA-4, a key immune suppressor.
  • A direct correlation was observed between CTLA-4 expression and Treg suppressive capacity.

Conclusions:

  • HDAC inhibitors are promising pharmacologic tools for augmenting Treg suppressive functions.
  • This approach may hold therapeutic potential for patients with autoimmune conditions or those undergoing transplantation.

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