Dendritic cells (DCs) are involved in regulating T-cell differentiation, and are thought to have an important role in inflammation associated with rheumatoid arthritis. The therapeutic generation of so-called tolerogenic DCs, which promote an anti-inflammatory cellular milieu in arthritic synovia, has become a lively area of research. Histone deacetylase (HDAC) inhibitors have previously been shown to have immunoregulatory and phenotype-altering effects on DCs. Consequently, Misaki et al. examined the effects of the HDAC inhibitor trichostatin A (TSA) in the SKG mouse model of T-cell-mediated chronic arthritis.

Subcutaneous injection of TSA dissolved in dimethyl sulfoxide (DMSO) for 28 days, starting 2 weeks after arthritis induction with zymosan A (before the onset of symptoms), resulted in significantly lower clinical and histological arthritis scores, compared with mice treated with DMSO alone, indicating a preventive effect of TSA against the development of arthritis. TSA treatment after arthritis onset also inhibited the worsening of clinical arthritis scores, compared with vehicle. TSA was shown to suppress the development of type 17 T helper cells and to promote regulatory-T-cell differentiation, and it decreased the expression of the co-stimulatory molecules CD86, CD80 and CD40 on the surface of splenic DCs. In vitro studies indicated that TSA inhibited zymosin-A-induced production of IL-12 and IL-6 by bone-marrow DCs.

These data indicate that HDAC inhibition ameliorates arthritis and promotes a tolerogenic phenotype in DCs in the SKG mouse model of arthritis. Further understanding of HDAC function in DCs might lead to the development of novel DC-targeting therapies.