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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 3/2011

Open Access 01-06-2011 | Research article

Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice

Authors: Kenta Misaki, Akio Morinobu, Jun Saegusa, Shimpei Kasagi, Masaaki Fujita, Yoshiaki Miyamoto, Fumichika Matsuki, Shunichi Kumagai

Published in: Arthritis Research & Therapy | Issue 3/2011

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Abstract

Introduction

The purpose of this study was to elucidate the effects of histone deacetylase inhibition on the phenotype and function of dendritic cells and on arthritis in SKG mice.

Methods

Arthritis was induced in SKG mice by zymosan A injection. Trichostatin A, a histone deacetylase inhibitor, was administered and its effects on arthritis were evaluated by joint swelling and histological evaluation. Interleukin-17 production in lymph node cells was determined by an enzyme-linked immunosorbent assay (ELISA). Foxp3 expression in lymph node cells and the phenotypes of splenic dendritic cells were examined by fluorescence-activated cell sorting (FACS). Bone marrow-derived dendritic cells (BM-DC) were generated with granulocyte macrophage colony-stimulating factor. The effects of trichostatin A on cell surface molecules, cytokine production, indoleamine 2,3-dioxygenase (IDO) expression and T cell stimulatory capacity were examined by FACS, ELISA, quantitative real-time polymerase chain reaction and Western blot, and the allo-mixed lymphocyte reaction, respectively.

Results

Trichostatin A, when administered before the onset of arthritis, prevented SKG mice from getting arthritis. Trichostatin A treatment also showed therapeutic effects on arthritis in SKG mice, when it was administered after the onset of arthritis. Trichostatin A treatment reduced Th17 cells and induced regulatory T cells in lymph node, and also decreased co-stimulatory molecule expression on splenic dendritic cells in vivo. In vitro, trichostatin A markedly suppressed zymosan A-induced interleukin-12 and interleukin-6 production by BM-DC and up-regulated IDO expression at mRNA and protein levels. Trichostatin A-treated BM-DC also showed less T cell stimulatory capacity.

Conclusions

Histone deacetylase inhibition changes dendritic cells to a tolerogenic phenotype and ameliorates arthritis in SKG mice.
Appendix
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Metadata
Title
Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice
Authors
Kenta Misaki
Akio Morinobu
Jun Saegusa
Shimpei Kasagi
Masaaki Fujita
Yoshiaki Miyamoto
Fumichika Matsuki
Shunichi Kumagai
Publication date
01-06-2011
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2011
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3339

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