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Clin Immunol. 2014 Mar;151(1):29-42. doi: 10.1016/j.clim.2014.01.002. Epub 2014 Jan 15.

Class I and II histone deacetylase inhibition by ITF2357 reduces SLE pathogenesis in vivo.

Author information

  • 1Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg VA, 24061, USA. Electronic address: appleton@vt.edu.
  • 2Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg VA, 24061, USA.
  • 3Department of Biotechnology, American University of Ras Al Khaimah, PO Box 10021, United Arab Emirates.
  • 4Department of Pathology, Center for Comparative Medicine Research, Wake Forest School of Medicine, Winston-Salem NC 27157, USA.
  • 5Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg VA, 24061, USA; Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, USA.

Abstract

We sought to determine if a specific class I and II HDAC inhibitor (ITF2357) was able to decrease disease in lupus-prone NZB/W mice through regulation of T cell profiles. From 22 to 38 weeks-of-age, NZB/W and non-lupus NZW mice were treated with ITF2357 (5 mg/kg or 10 mg/kg), or vehicle control. Body weight and proteinuria were measured every 2 weeks, while sera anti-dsDNA and cytokine levels were measured every 4 weeks. Kidney disease was determined by sera IgG levels, immune complex deposition, and renal pathology. T lymphocyte profiles were assessed using flow cytometric analyses. Our results showed that NZB/W mice treated with the 10 mg/kgof ITF2357 had decreased renal disease and inflammatory cytokines in the sera. Treatment with ITF2357 decreased the Th17 phenotype while increasing the percentage of Tregs as well as Foxp3 acetylation. These results suggest that specific HDAC inhibition may decrease disease by altering T cell differentiation and acetylation.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Histone deacetylase; Regulatory T cells; Systemic lupus erythematosus

PMID:
24503172
[PubMed - indexed for MEDLINE]
PMCID:
PMC3963170
Free PMC Article
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