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 con...

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Published in:	Clinical immunology (Orlando, Fla.) Vol. 151; no. 1; pp. 29 - 42
Main Authors:	Regna, Nicole L, Chafin, Cristen B, Hammond, Sarah E, Puthiyaveetil, Abdul G, Caudell, David L, Reilly, Christopher M
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2014
Subjects:	Acetylation Allergy and Immunology Animals Antibodies, Antinuclear - biosynthesis Antibodies, Antinuclear - immunology Body Weight - drug effects Cell Differentiation DNA - immunology Drug Administration Schedule Female Forkhead Transcription Factors - immunology Forkhead Transcription Factors - metabolism Histone deacetylase Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - immunology Histone Deacetylases - metabolism Hydroxamic Acids - pharmacology Immunoglobulin G - biosynthesis Immunoglobulin G - immunology Kidney - drug effects Kidney - immunology Kidney - metabolism Kidney - pathology Lupus Erythematosus, Systemic - drug therapy Lupus Erythematosus, Systemic - immunology Lupus Erythematosus, Systemic - metabolism Lupus Erythematosus, Systemic - pathology Mice Mice, Inbred NZB Proteinuria - prevention & control Regulatory T cells Systemic lupus erythematosus T-Lymphocyte Subsets - drug effects T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - pathology Regulatory T cells Histone deacetylase Systemic lupus erythematosus
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Summary:	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 10mg/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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1521-6616 1521-7035
DOI:	10.1016/j.clim.2014.01.002