The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice

Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

“…These observations are in accordance with a number of studies that have shown that TSA upregulates Treg cell functions in NZB/W F1 ( 36 ) and Balb/c mice ( 37 ). Nonetheless, in both the studies, TSA failed to infl uence the IL-2 gene expression and, therefore, to reverse the Treg cell anergy ( 36,37 ). As far as DHA is concerned, we observed that DHA diminished the upregulated TSAinduced Treg activity, though this fatty acid could not completely reverse the Treg activity.…”

HDAC Inhibition in Lupus Models

“…Autoantibodies are a hallmark of lupus nephritis; studies by van Bavel et al reported that elevated autoantibody production was observed in acetylated apoptotic cells compared with nonacetylated apoptotic cells (101). This would suggest acetylation may increase autoantibody production in lupus; we found in our studies that lupus mice treated with TSA did not show a decreased production of autoantibodies (69). It may be somewhat surprising that autoantibody production was not decreased with HDAC inhibition.…”

“…Subsequently these animals develop systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, arthritis and immune complex glomerulonephritis similar to human lupus and die at around 24 weeks from renal disease. The composite genome distribution of autoantibodies produced by these mice are similar in spectrum to those seen in human lupus including anti-double-stranded DNA antibodies and anti-Sm antibodies (51,52 Using two HDACi (TSA and SAHA), we have demonstrated that these agents decrease kidney disease in both the MRL/lpr and NZB/NZW F1 mice lupus mouse models (67)(68)(69). In MRL/lpr mice, we demonstrated that TSA and SAHA decreased inflammatory cytokine (IL-12, IFN-γ, IL-6 and IL-10) production in isolated splenocytes while increasing accumulation of acetylated histones H3 and H4 in total cellular chromatin.…”

“…+ (Treg) cells (69). This may be important in the pathogenesis of SLE, as human studies have demonstrated the numbers of Treg cells in SLE patients was related inversely to both the serum level of anti-dsDNA and disease activity (72,73).…”

Inhibition of Histone Deacetylases in Inflammatory Bowel Diseases

“…Inhibition of HSP70 reduced the antiinflammatory efficacy of HDAC9-knockout Tregs, while Tregs that overexpressed HSP70 exerted an enhanced suppressive function (39). The therapeutic potency of manipulating FoxP3 acetylation via class II HDAC inhibition could be confirmed in other inflammatory models such as transplant rejection or arthritis (37,39,71,72).…”