HDAC Inhibitors: Novel Immunosuppressants for Allo‐ and Xeno‐ Transplantation

Abstract

Immune rejection is the major obstacle to graft survival and quality of life of recipients after organ transplantation. The immunosuppressants applied in clinical face severe safety and efficacy issues. Histone deacetylases (HDACs) are emerging novel drug targets in the treatment of malignancies and immune disorders. HDAC inhibitors show potential as valuable immune regulators after allo-or xeno-organ transplantation. However, studies that evaluate HDAC inhibitors and mechanisms are still limited. In this review, we focused on the immunomodulatory effects of HDAC inhibitors in transplantation. Finally, we discussed the implications and challenges of applying HDAC inhibitors in allo-and xeno-transplantation.

Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight

“…Panobinostat, aside from its approval in multiple myeloma, is under investigation as an immunomodulator for graft-versus-host diseases following allogeneic hematopoietic stem cell transplantation. 83 Outside oncology, vorinostat is in early studies for the treatment of epilepsy 84 and Cushing's disease. 85…”

Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas

“…Histone deacetylases are a class of enzymes deacetylating the acetyl group from ε-N-acetyl lysine amino acid from a histone, which lead to the tight wrapping of DNA. HDACs play a key role in the homeostasis maintenances of histone acetylation euchromatin and heterochromatin in living system 9 , 10 . There are 18 HDACs recognized up to now, divided into HDAC I (HDAC 1, 2, and 3: mainly in the nucleus; HDAC 8: partially in the cytoplasm), HDAC II (HDAC 4, 5, 6, 7, 9, and 10: shuttling in and out of the nucleus), as Table 1 showed 11 .…”

Promising drug repurposing approach targeted for cytokine storm implicated in SARS-CoV-2 complications

“…Histone deacetylases (HDACs) are a class of enzymes that remove the acetyl moiety from specific lysine residues on histone proteins leading to the tight wrapping of DNA. Therefore, HDACs act as key epigenetic modulators of essentially biological processes including transcription factors, chaperones and signaling molecules, resulting in changes in protein stability, protein-protein interactions, and protein-DNA interactions to control diverse cell functions [ 115 , 116 ].…”