Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells

Abstract

Genetic changes are difficult to reverse; thus, epigenetic aberrations, including changes in DNA methylation, histone modifications, and noncoding RNAs, with potential reversibility, have attracted attention as pharmaceutical targets. The current paradigm is that histone deacetylases (HDACs) regulate gene expression via deacetylation of histone and nonhistone proteins or by forming corepressor complexes with transcription factors. The emergence of epigenetic tools related to HDACs can be used as diagnostic and therapeutic markers. HDAC inhibitors that block specific or a series of HDACs have proven to be a powerful therapeutic treatment for immune-related diseases. Here, we summarize the various roles of HDACs and HDAC inhibitors in the development and function of innate and adaptive immune cells and their implications for various diseases and therapies.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis

“…We also found that XQLD could downregulate the expression of HDAC1, HDAC3, and HDAC4. HDAC has been recognized it is closely related to immune regulation and can regulate the innate and adaptative immune response [20,21]. Recently, HDAC has been found it could also regulate the proliferation of type 2 innate lymphoid cells in airway inflammation [22] and modulate effector T cell phenotypes in severe COVID-19 patients [23].…”

Histone deacetylase-mediated tumor microenvironment characteristics and synergistic immunotherapy in gastric cancer

“…Studies have shown that HDAC regulators play an indispensable role in regulating the TME [17,38]. Most previous studies have explored the function of a single HDAC or a class of HDACs, but different HDACs play highly heterogeneous roles in regulating the TME and antitumor effects [38][39][40].…”

“…Conversely, deacetylation of histones has the opposite effect [14]. HDACs reversibly regulate the acetylation status of histones and nonhistone proteins during TME development [15][16][17]. Moreover, HDAC6 is involved in the upregulation of several key factors in the immune system, such as PD-1 and PD-L1 receptors, which are the main cancer immunotherapy targets [18].…”

Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification

“…Meanwhile, the level of HDAC11 correlates with the function of neutrophils. Neutrophils lacking HDAC11 are better able to cope with LPS-induced sepsis, granulocyte expansion, and increased extramedullary hematopoiesis, showing increased migration of inflammatory cytokines and phagocytosis [ 101 , 102 ]. The use of different concentrations of HDAC inhibitors (HDACis), belinostat, and panobinostat, to promote histone acetylation revealed a shift in the type of neutrophil death from NETosis to apoptosis.…”