scholarly journals Combination of IL-2, rapamycin, DNA methyltransferase and histone deacetylase inhibitors for the expansion of human regulatory T cells

Oncotarget ◽  
2016 ◽  
Vol 8 (62) ◽  
pp. 104733-104744 ◽  
Author(s):  
Makoto Miyara ◽  
Driss Chader ◽  
Aude Burlion ◽  
Jérémie Goldstein ◽  
Delphine Sterlin ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Histone Deacetylase Inhibitors

Induction of Foxp3+ regulatory T cells with histone deacetylase inhibitors

2009 ◽  
Vol 257 (1-2) ◽  
pp. 97-104 ◽  
Author(s):  
Julie L. Lucas ◽  
Parham Mirshahpanah ◽  
Eric Haas-Stapleton ◽  
Khusru Asadullah ◽  
Thomas M. Zollner ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors

Arsenite induces dysfunction of regulatory T cells through acetylation control of the Foxp3 promoter

2020 ◽  
Vol 40 (1) ◽  
pp. 35-46
Author(s):  
J Chen ◽  
J Jiang ◽  
Y Liu ◽  
Y Ye ◽  
Y Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Histone Deacetylase Inhibitors ◽  
Lymphocyte Subsets ◽  
Trichostatin A ◽  
Human Lymphocytes ◽  
Histone H4 ◽  
T Lymphocyte Subsets ◽  
Winged Helix ◽  
Protein Levels

Arsenic is known to cause damage to the body’s immune system by inducing epigenetic changes. However, the molecular mechanism of this damage remains elusive. Here, we report that arsenic disrupts the morphology of lymphocytes, decreases cell viability, and results in abnormal proportions of T lymphocyte subsets. Moreover, our results revealed that arsenic can reduce global acetylation of histone H4 at K16 (H4K16 ac) in lymphocytes via decreasing the level of males absent on the first but upregulates mRNA and protein levels of the forkhead/winged-helix box P3 ( Foxp3) gene by increasing the acetylation of histone H4 at K16 (H4K16) at the promoter of Foxp3. Finally, arsenic-induced dysfunction of regulatory T cells (Tregs) could be ameliorated by trichostatin A. Our research indicates that arsenic-induced immunosuppressive effect in human lymphocytes may be related to the acetylation of H4K16 at the promoter of Foxp3 and that histone deacetylase inhibitors may play a role in the prevention and treatment of immune injury caused by arsenic.

The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice

2010 ◽  
Vol 5 (2) ◽  
pp. 201-220 ◽  
Author(s):  
Gang Wang ◽  
Stephen F Badylak ◽  
Ellen Heber-Katz ◽  
Susan J Braunhut ◽  
Lorraine J Gudas
Keyword(s):  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Histone Deacetylase Inhibitors ◽  
Dna Methyltransferase Inhibitors ◽  
Digit Regeneration

Six (or More) Drugs in Search of a Mechanism: DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes

2006 ◽  
Vol 4 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Steven D. Gore
Keyword(s):  
Histone Deacetylase ◽  
Myelodysplastic Syndromes ◽  
Dna Methyltransferase ◽  
Histone Deacetylase Inhibitors ◽  
Conclusive Evidence ◽  
Clinical Activity ◽  
Dna Methyltransferase Inhibitors ◽  
Expression Of Genes ◽  
Measurable Activity ◽  
Epigenetic Modulation

The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and 2′-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that epigenetic modulation of gene transcription may play an important pathogenetic role in the development and expression of these diseases. Approximately 50% of patients treated with these compounds experience hematologic improvement, making these the most active single agents for unselected patients with MDS. Responses include complete and partial hematologic responses. Two randomized trials have shown that the use of these drugs significantly alters the natural history of MDS compared with supportive care. Histone deacetylase inhibitors, which may also impact the expression of genes through epigenetic mechanisms, seem to have measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors are most likely used in combination with other agents, including DNA methyltransferase inhibitors. Despite the clinical activity of these classes of drugs, there is no conclusive evidence that their clinical activity is attributable to their impact on the epigenome. Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS.

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