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Molecular Medicine

, Volume 17, Issue 5–6, pp 417–425 | Cite as

HDAC Inhibition in Lupus Models

  • Christopher M Reilly
  • Nicole Regna
  • Nilamadhab Mishra
Review Article

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune inflammatory disease characterized by the production of autoantibodies directed against nuclear antigens such as nucleosomes, DNA and histone proteins found within the body’s cells and plasma. Autoantibodies may induce disease by forming immune complexes that lodge in target organs or by crossreacting with targeted antigens and damaging tissue. In addition to autoantibody production, apoptotic defects and impaired removal of apoptotic cells contribute to an overload of autoantigens that initiate an autoimmune response. Besides the well-recognized genetic susceptibility to SLE, environmental and epigenetic factors play a crucial role in disease pathogenesis as evidenced by monozygotic twins typically being discordant for disease. Changes in DNA methylation and histone acetylation alter gene expression and are thought to contribute to the epigenetic deregulation in disease. In SLE, global and gene-specific DNA methylation changes have been demonstrated to occur. Additionally, aberrant histone acetylation is evident in individuals with SLE. Moreover, histone deacetylase inhibitors (HDACi) have been shown to reverse the skewed expression of multiple genes involved in SLE. In this review, we discuss the implications of epigenetic alterations in the development and progression of SLE, and how therapeutics designed to alter histone acetylation status may constitute a promising avenue to target disease.

Notes

Acknowledgments

The authors would like to thank C Dinarello for his insightful comments with the manuscript.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Christopher M Reilly
    • 1
    • 3
  • Nicole Regna
    • 1
  • Nilamadhab Mishra
    • 2
  1. 1.Virginia-Maryland Regional College of Veterinary MedicineVirginia Polytechnic Institute and State UniversityBlacksburgUSA
  2. 2.Wake Forest University Baptist Medical CenterWinston-SalemUSA
  3. 3.Virginia College of Osteopathic MedicineBlacksburgUSA

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