title: Class I and II histone deacetylase inhibition by ITF2357 reduces SLE pathogenesis in vivo.
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.
authors: Department 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.
authors: Nicole L
authors: NL
authors: Regna
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg VA, 24061, USA.
authors: Cristen B
authors: CB
authors: Chafin
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg VA, 24061, USA.
authors: Sarah E
authors: SE
authors: Hammond
authors: Department of Biotechnology, American University of Ras Al Khaimah, PO Box 10021, United Arab Emirates.
authors: Abdul G
authors: AG
authors: Puthiyaveetil
authors: Department of Pathology, Center for Comparative Medicine Research, Wake Forest School of Medicine, Winston-Salem NC 27157, USA.
authors: David L
authors: DL
authors: Caudell
authors: Department 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.
authors: Christopher M
authors: CM
authors: Reilly
mesh_terms: D000107:Acetylation; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation; D004247:DNA / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007074:Immunoglobulin G; D004247:DNA; D006655:Histone Deacetylases; C502418:givinostat hydrochloride
keywords: Histone deacetylase; Regulatory T cells; Systemic lupus erythematosus