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


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.



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


  1. 1.
    Shapira Y, Agmon-Levin N, Shoenfeld Y. (2010) Defining and analyzing geoepidemiology and human autoimmunity. J.Autoimmun. 34:J168–77.CrossRefGoogle Scholar
  2. 2.
    Hahn BH. (2003) Systemic lupus erythematosus and accelerated atherosclerosis. N. Engl. J. Med. 349:2379–80.CrossRefGoogle Scholar
  3. 3.
    Centola M, et al. (2007) Gene expression profiles of systemic lupus erythematosus and rheumatoid arthritis. Expert Rev. Clin. Immunol. 3:797–806.CrossRefGoogle Scholar
  4. 4.
    Bruce IN. (2005) Atherogenesis and autoimmune disease: the model of lupus. Lupus. 14:687–690.CrossRefGoogle Scholar
  5. 5.
    Valesini G, Conti F. (2011) The persistent challenge of lupus nephritis. Clin. Rev. Allergy Immunol. 40:135–7.CrossRefGoogle Scholar
  6. 6.
    Daikh DI, Wofsy D. (1998) On the horizon: clinical trials of new immunosuppressive strategies for autoimmune diseases. Transplant. Proc. 30:4027–8.CrossRefGoogle Scholar
  7. 7.
    Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. (2010) The geoepidemiology of systemic lupus erythematosus. Autoimmun. Rev. 9:A277–87.CrossRefGoogle Scholar
  8. 8.
    Aran AA, Putterman C. (2008) Treatment of lupus nephritis: facing the era of immunotherapy. Panminerva Med. 50:235–45.PubMedGoogle Scholar
  9. 9.
    Giles I, Putterman C. (2008) Autoantibodies and other biomarkers — pathological consequences (1). Lupus. 17:241–246.CrossRefGoogle Scholar
  10. 10.
    La Cava A. Targeting B cells with biologics in systemic lupus erythematosus. Expert Opin. Biol. Ther. 10:1555–61.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Burmester GR, Horneff G, Emmrich F. (1992) Management of early inflammatory arthritis. Intervention with immunomodulatory agents: monoclonal antibody therapy. Baillieres Clin. Rheumatol. 6:415–34.CrossRefGoogle Scholar
  12. 12.
    Choi JK. (2010) Systems biology and epigenetic gene regulation. IET Syst. Biol. 4:289.CrossRefGoogle Scholar
  13. 13.
    Selvi BR, Krishna DV, Ostwal YB, Kundu TK. (2010) Small molecule modulators of histone acetylation and methylation: a disease perspective. Biochim. Biophys. Acta. 1799:810–28.CrossRefGoogle Scholar
  14. 14.
    Perl A. (2010) Pathogenic mechanisms in systemic lupus erythematosus. Autoimmunity. 43:1–6.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Willyard C. (2010) The saving switch. Nat. Med. 16:18–21.CrossRefGoogle Scholar
  16. 16.
    Karberg S. (2009) Switching on epigenetic therapy. Cell. 139:1029–31.CrossRefGoogle Scholar
  17. 17.
    Marks PA. (2007) Discovery and development of SAHA as an anticancer agent. Oncogene. 26:1351–6.CrossRefGoogle Scholar
  18. 18.
    McGee-Lawrence ME, Westendorf JJ. (2011) Histone deacetylases in skeletal development and bone mass maintenance. Gene. 474:1–11.CrossRefGoogle Scholar
  19. 19.
    Montgomery RL, et al. (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes. Dev. 21:1790–802.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Montgomery RL, et al. (2008) Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. J. Clin. Invest. 118:3588–97.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Haberland M, Mokalled MH, Montgomery RL, Olson EN. (2009) Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes. Dev. 23:1625–30.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Zhang K, et al. (2002) Histone acetylation and deacetylation: identification of acetylation and methylation sites of HeLa histone H4 by mass spectrometry. Mol. Cell. Proteomics. 1:500–8.CrossRefGoogle Scholar
  23. 23.
    Chang S, et al. (2006) Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell. 126:321–34.CrossRefGoogle Scholar
  24. 24.
    de Zoeten EF, Wang L, Sai H, Dillmann WH, Hancock WW. Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology. 138:583–94.Google Scholar
  25. 25.
    Zhou X, Marks PA, Rifkind RA, Richon VM. (2001) Cloning and characterization of a histone deacetylase, HDAC9. Proc. Natl. Acad. Sci. U. S. A. 98:10572–7.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Glauben R, Siegmund B. (2009) Molecular basis of histone deacetylase inhibitors as new drugs for the treatment of inflammatory diseases and cancer. Methods Mol. Biol. 512:365–76.CrossRefGoogle Scholar
  27. 27.
    Blanchard F, Chipoy C. (2005) Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov. Today. 10:197–204.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Guardiola AR, Yao TP. (2002) Molecular cloning and characterization of a novel histone deacetylase HDAC10. J. Biol. Chem. 277:3350–6.CrossRefGoogle Scholar
  29. 29.
    Dangond F, Gullans SR. (1998) Differential expression of human histone deacetylase mRNAs in response to immune cell apoptosis induction by trichostatin A and butyrate. Biochem. Biophys. Res. Commun. 247:833–7.CrossRefGoogle Scholar
  30. 30.
    Chavan AV, Somani RR. (2010) HDAC inhibitors — new generation of target specific treatment. Mini Rev. Med. Chem. 10:1263–76.CrossRefGoogle Scholar
  31. 31.
    Beumer JH, Tawbi H. (2010) Role of histone deacetylases and their inhibitors in cancer biology and treatment. Curr. Clin. Pharmacol 5:196–208.CrossRefGoogle Scholar
  32. 32.
    Rambaldi A, et al. (2010) A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br. J. Haematol. 150:446–55.PubMedGoogle Scholar
  33. 33.
    Balomenos D, Rumold R, Theofilopoulos AN. (1998) Interferon-gamma is required for lupuslike disease and lymphoaccumulation in MRL-lpr mice. J. Clin. Invest. 101:364–71.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Jevnikar AM, Grusby MJ, Glimcher LH. (1994) Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. J. Exp. Med. 179:1137–43.CrossRefGoogle Scholar
  35. 35.
    Baechler EC, Gregersen PK, Behrens TW. (2004) The emerging role of interferon in human systemic lupus erythematosus. Curr. Opin. Immunol. 16:801–7.PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Lemay S, Mao C, Singh AK. (1996) Cytokine gene expression in the MRL/lpr model of lupus nephritis. Kidney Int. 50:85–93.CrossRefGoogle Scholar
  37. 37.
    Hemminki K, Li X, Sundquist J, Sundquist K. (2009) Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis Rheum. 60:661–8.CrossRefGoogle Scholar
  38. 38.
    Fong KY, Boey ML. (1998) The genetics of systemic lupus erythematosus. Ann. Acad. Med. Singapore. 27:42–6.PubMedGoogle Scholar
  39. 39.
    Javierre BM, et al. (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res. 20:170–9.PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Ballestar E, Esteller M, Richardson BC. (2006) The epigenetic face of systemic lupus erythematosus. J. Immunol. 176:7143–7.CrossRefGoogle Scholar
  41. 41.
    Litwin A, Adams LE, Zimmer H, Hess EV. (1981) Immunologic effects of hydralazine in hypertensive patients. Arthritis Rheum. 24:1074–8.CrossRefGoogle Scholar
  42. 42.
    Uetrecht JP, Freeman RW, Woosley RL. (1981) The implications of procainamide metabolism to its induction of lupus. Arthritis Rheum. 24:994–1003.CrossRefGoogle Scholar
  43. 43.
    Marsden JR, Mason GG, Coburn PR, Rawlins MD, Shuster S. (1985) Drug acetylation and expression of lupus erythematosus. Eur. J. Clin. Pharmacol. 28:387–90.CrossRefGoogle Scholar
  44. 44.
    Portanova JP, Small CJ, Kohler PF. (1985) No demonstrable relationship between IgM and IgG antinuclear antibody levels and acetylator phenotype in patients with systemic lupus erythematosus. Arthritis Rheum. 28:995–8.CrossRefGoogle Scholar
  45. 45.
    Mongey AB, Sim E, Risch A, Hess E. (1999) Acetylation status is associated with serological changes but not clinically significant disease in patients receiving procainamide. J. Rheumatol. 26:1721–6.PubMedGoogle Scholar
  46. 46.
    Andrews BS, et al. (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J. Exp. Med. 148:1198–215.CrossRefGoogle Scholar
  47. 47.
    Bouzahzah F, Jung S, Craft J. (2003) CD4+ T cells from lupus-prone mice avoid antigen-specific tolerance induction in vivo. J. Immunol. 170:741–8.CrossRefGoogle Scholar
  48. 48.
    Chan O, Madaio MP, Shlomchik MJ. (1997) The roles of B cells in MRL/lpr murine lupus. Ann. N. Y. Acad. Sci. 815:75–87.CrossRefGoogle Scholar
  49. 49.
    Chan OT, Madaio MP, Shlomchik MJ. (1999) B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity. J. Immun. 163:3592–6.PubMedGoogle Scholar
  50. 50.
    Cohen PL, Eisenberg RA. (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol. 9:243–69.CrossRefGoogle Scholar
  51. 51.
    Theofilopoulos AN, Dixon FJ. (1985) Murine models of systemic lupus erythematosus. Adv. Immunol. 37:269–390.CrossRefGoogle Scholar
  52. 52.
    Theofilopoulos AN, Kono DH. (1998) Mechanisms and genetics of autoimmunity. Ann. N. Y. Acad. Sci. 841:225–35.CrossRefGoogle Scholar
  53. 53.
    Fairhurst AM, et al. (2009) Type I interferons produced by resident renal cells may promote endorgan disease in autoantibody-mediated glomerulonephritis. J. Immunol. 183:6831–8.PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Zeller GC, Hirahashi J, Schwarting A, Sharpe AH, Kelley VR. (2006) Inducible co-stimulator null MRL-Faslpr mice: uncoupling of autoantibodies and T cell responses in lupus. J. Am. Soc. Nephrol. 17:122–30.CrossRefGoogle Scholar
  55. 55.
    Odegard JM, et al. (2009) ICOS controls effector function but not trafficking receptor expression of kidney-infiltrating effector T cells in murine lupus. J. Immunol. 182:4076–84.PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Vinuesa CG, Sanz I, Cook MC. (2009) Dysregulation of germinal centres in autoimmune disease. Nat. Rev. Immunol. 9:845–57.CrossRefGoogle Scholar
  57. 57.
    DiPlacido LD, Craft J. (2010) Emerging from the shadows: follicular helper T cells in autoimmunity. Arthritis Rheum. 62:6–8.PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Simpson N, et al. (2010) Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum. 62:234–44.CrossRefGoogle Scholar
  59. 59.
    Yan XJ, et al. (2009) Indole-3-carbinol improves survival in lupus-prone mice by inducing tandem B- and T-cell differentiation blockades. Clin. Immunol. 131:481–94.CrossRefGoogle Scholar
  60. 60.
    Valencia X, Yarboro C, Illei G, Lipsky PE. (2007) Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J. Immunol. 178:2579–88.CrossRefGoogle Scholar
  61. 61.
    Miyara M, et al. (2005) Global natural regulatory T cell depletion in active systemic lupus erythematosus. J. Immunol. 175:8392–400.CrossRefGoogle Scholar
  62. 62.
    Gerli R, et al. (2009) Identification of regulatory T cells in systemic lupus erythematosus. Autoimmun. Rev. 8:426–30.CrossRefGoogle Scholar
  63. 63.
    Iliopoulos D, Oikonomou P, Messinis I, Tsezou A. (2009) Correlation of promoter hypermethylation in hTERT, DAPK and MGMT genes with cervical oncogenesis progression. Oncol. Rep. 22:199–204.PubMedGoogle Scholar
  64. 64.
    Iliopoulos D, Satra M, Drakaki A, Poultsides GA, Tsezou A. (2009) Epigenetic regulation of hTERT promoter in hepatocellular carcinomas. Int. J. Oncol. 34:391–9.PubMedGoogle Scholar
  65. 65.
    Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. (2009) An operational definition of epigenetics. Genes. Dev. 23:781–3.PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Garcia BA, Busby SA, Shabanowitz J, Hunt DF, Mishra N. (2005) Resetting the epigenetic histone code in the MRL-lpr/lpr mouse model of lupus by histone deacetylase inhibition. J. Proteome Res. 4:2032–42.CrossRefGoogle Scholar
  67. 67.
    Reilly CM, et al. (2004) Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. J. Immunol. 173:4171–8.CrossRefGoogle Scholar
  68. 68.
    Mishra N, Reilly CM, Brown DR, Ruiz P, Gilkeson GS. (2003) Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J. Clin. Invest. 111:539–52.PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Reilly CM, et al. (2008) The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice. J. Autoimmun. 31:123–30.PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Susick L, Senanayake T, Veluthakal R, Woster PM, Kowluru A. (2009) A novel histone deacetylase inhibitor prevents IL-1beta induced metabolic dysfunction in pancreatic beta-cells. J. Cell Mol. Med. 13:1877–85.PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Voronov E, et al. (2006) IL-1 beta-deficient mice are resistant to induction of experimental SLE. Eur. Cytokine Netw. 17:109–16.PubMedGoogle Scholar
  72. 72.
    Horwitz DA. (2008) Regulatory T cells in systemic lupus erythematosus: past, present and future. Arthritis Res. Ther. 10:227.PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Bonelli M, von Dalwigk K, Savitskaya A, Smolen JS, Scheinecker C. (2008) Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus (SLE): a comparative phenotypic analysis. Ann. Rheum. Dis. 67:664–71.CrossRefGoogle Scholar
  74. 74.
    Shuttleworth SJ, Bailey SG, Townsend PA. (2010) Histone deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr. Drug Targets. 11:1430–8.CrossRefGoogle Scholar
  75. 75.
    Glauben R, et al. (2006) Histone hyperacetylation is associated with amelioration of experimental colitis in mice. J. Immunol. 176:5015–22.CrossRefGoogle Scholar
  76. 76.
    Tao R, et al. (2007) Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med. 13:1299–307.CrossRefGoogle Scholar
  77. 77.
    Tao R, et al. (2007) Histone deacetylase inhibitors and transplantation. Curr. Opin. Immunol. 19:589–95.PubMedCentralCrossRefPubMedGoogle Scholar
  78. 78.
    Mok MY, Wu HJ, Lo Y, Lau CS. The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease activity in systemic lupus erythematosus. J. Rheumatol. 37:2046–52.CrossRefGoogle Scholar
  79. 79.
    Ma J, et al. (2010) The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients. Clin. Rheumatol. 29:1251–8.CrossRefGoogle Scholar
  80. 80.
    Bosisio D, et al. (2008) Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo. J. Leukoc. Biol. 84:1540–8.PubMedCentralCrossRefPubMedGoogle Scholar
  81. 81.
    Lit LC, et al. (2007) Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus. J. Rheumatol. 34:89–96.PubMedGoogle Scholar
  82. 82.
    Sun D, et al. (2004) Regulation of immune function by calorie restriction and cyclophosphamide treatment in lupus-prone NZB/NZW F1 mice. Cell. Immunol. 228:54–65.CrossRefGoogle Scholar
  83. 83.
    Crispin JC, et al. (2003) Immunoregulatory defects in patients with systemic lupus erythematosus in clinical remission. Lupus. 12:386–93.CrossRefGoogle Scholar
  84. 84.
    Enghard P, Langnickel D, Riemekasten G. (2006) T cell cytokine imbalance towards production of IFN-gamma and IL-10 in NZB/W F1 lupus-prone mice is associated with autoantibody levels and nephritis. Scand. J. Rheumatol. 35:209–16.CrossRefGoogle Scholar
  85. 85.
    Kikawada E, Lenda DM, Kelley VR. (2003) IL-12 deficiency in MRL-Fas(lpr) mice delays nephritis and intrarenal IFN-gamma expression, and diminishes systemic pathology. J. Immunol. 170:3915–25.CrossRefGoogle Scholar
  86. 86.
    Raziuddin S, al-Janadi MA, al-Wabel AA. (1991) Soluble interleukin 2 receptor levels in serum and its relationship to T cell abnormality and clinical manifestations of the disease in patients with systemic lupus erythematosus. J. Rheumatol. 18:831–6.PubMedGoogle Scholar
  87. 87.
    Toubi E, Shoenfeld Y. (2004) The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pathway. Autoimmunity. 37:457–64.CrossRefGoogle Scholar
  88. 88.
    Todoerti K, et al. (2010) Pleiotropic anti-myeloma activity of ITF2357: inhibition of interleukin-6 receptor signaling and repression of miR-19a and miR-19b. Haematologica. 95:260–9.CrossRefGoogle Scholar
  89. 89.
    Glauben R, et al. (2008) Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice. Gut. 57:613–22.CrossRefGoogle Scholar
  90. 90.
    Shein NA, et al. (2009) Histone deacetylase inhibitor ITF2357 is neuroprotective, improves functional recovery, and induces glial apoptosis following experimental traumatic brain injury. FASEB J. 23:4266–75.PubMedCentralCrossRefPubMedGoogle Scholar
  91. 91.
    Faraco G, et al. (2009) Histone deacetylase (HDAC) inhibitors reduce the glial inflammatory response in vitro and in vivo. Neurobiol. Dis. 36:269–79.PubMedCentralCrossRefPubMedGoogle Scholar
  92. 92.
    Illei GG, et al. (2010) Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 62:542–52.PubMedCentralCrossRefPubMedGoogle Scholar
  93. 93.
    Salvi V, et al. (2010) Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells. Immunobiology. 215:756–61.CrossRefGoogle Scholar
  94. 94.
    Reddy P, et al. (2008) Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice. J. Clin. Invest. 118:2562–73.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Nambiar MP, Warke VG, Fisher CU, Tsokos GC. (2002) Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling. J. Cell. Biochem. 85:459–69.CrossRefGoogle Scholar
  96. 96.
    Kircher B, Latzer K, Gastl G, Nachbaur D. (2003) Comparative in vitro study of the immunomodulatory activity of humanized and chimeric anti-CD25 monoclonal antibodies. Clin. Exp. Immunol. 134:426–30.PubMedCentralCrossRefPubMedGoogle Scholar
  97. 97.
    Li N, et al. (2008) HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen. Proc. Natl. Acad. Sci. U. S. A. 105:4796–801.PubMedCentralCrossRefPubMedGoogle Scholar
  98. 98.
    Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D. (1994) The role of B cells in lpr/lpr-induced autoimmunity. J. Exp. Med. 180:1295–306.CrossRefGoogle Scholar
  99. 99.
    Ye YL, Suen JL, Chen YY, Chiang BL. (1998) Phenotypic and functional analysis of activated B cells of autoimmune NZB x NZW F1 mice. Scand. J. Immunol. 47:122–6.CrossRefGoogle Scholar
  100. 100.
    Lu ZP, Ju ZL, Shi GY, Zhang JW, Sun J. (2005) Histone deacetylase inhibitor Trichostatin A reduces anti-DNA autoantibody production and represses IgH gene transcription. Biochem. Biophys. Res. Commun. 330:204–9.CrossRefGoogle Scholar
  101. 101.
    van Bavel CC, Dieker JW, Tamboer WP, van der Vlag J, Berden JH. (2010) Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize acetylated conformational epitopes. Mol. Immunol. 48:248–56.CrossRefGoogle Scholar
  102. 102.
    Ahuja A, et al. (2007) Depletion of B cells in murine lupus: efficacy and resistance. J. Immunol. 179:3351–61.CrossRefGoogle Scholar
  103. 103.
    Haas KM, et al. (2010) Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice. J. Immunol. 184:4789–800.PubMedCentralCrossRefPubMedGoogle Scholar
  104. 104.
    Baechler EC, et al. (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. U. S. A. 100:2610–5.PubMedCentralCrossRefPubMedGoogle Scholar
  105. 105.
    Bleesing JJ, et al. (2001) Immunophenotypic profiles in families with autoimmune lymphopro-liferative syndrome. Blood. 98:2466–73.CrossRefGoogle Scholar
  106. 106.
    North BJ, Verdin E. (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol. 5:224.PubMedCentralCrossRefPubMedGoogle Scholar
  107. 107.
    Imai S, Armstrong CM, Kaeberlein M, Guarente L. (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 403:795–800.CrossRefGoogle Scholar
  108. 108.
    Hu N, Long H, Zhao M, Yin H, Lu Q. (2009) Aberrant expression pattern of histone acetylation modifiers and mitigation of lupus by SIRT1-siRNA in MRL/lpr mice. Scand. J. Rheumatol. 38:464–71.CrossRefGoogle Scholar
  109. 109.
    Hu N, et al. (2008) Abnormal histone modification patterns in lupus CD4+ T cells. J. Rheumatol. 35:804–10.PubMedGoogle Scholar
  110. 110.
    Kuwatsuka Y, et al. (2009) Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis. Autoimmunity. 42:120–5.CrossRefGoogle Scholar
  111. 111.
    Crow MK. (2008) Collaboration, genetic associations, and lupus erythematosus. N. Engl. J. Med. 358:956–61.CrossRefGoogle Scholar
  112. 112.
    Liu K, Mohan C. (2006) What do mouse models teach us about human SLE? Clin. Immunol. 119:123–30.CrossRefGoogle Scholar
  113. 113.
    Sedighi M, Sengupta AM. (2007) Epigenetic chromatin silencing: bistability and front propagation. Phys. Biol. 4:246–55.PubMedCentralCrossRefPubMedGoogle Scholar
  114. 114.
    Guerini V, et al. (2008) The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F). Leukemia. 22:740–7.CrossRefGoogle Scholar
  115. 115.
    Vojinovic J, Damjanov N. (2011) HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol. Med. 17:397–403.PubMedCentralCrossRefPubMedGoogle Scholar
  116. 116.
    Bauer JW, Bilgic H, Baechler EC. (2009) Geneexpression profiling in rheumatic disease: tools and therapeutic potential. Nat. Rev. Rheumatol. 5:257–65.CrossRefGoogle Scholar
  117. 117.
    van Baarsen LG, Bos CL, van der Pouw Kraan TC, Verweij CL. (2009) Transcription profiling of rheumatic diseases. Arthritis Res. Ther. 11:207.PubMedCentralCrossRefPubMedGoogle Scholar
  118. 118.
    Thanou-Stavraki A, Sawalha AH. (2011) An update on belimumab for the treatment of lupus. Biologics. 5:33–43.PubMedCentralPubMedGoogle Scholar

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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