The role of histone deacetylases in inflammatory respiratory diseases: an update

ABSTRACT

Introduction

Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues of histones and other proteins, generally leading to a closed chromosomal configuration and transcriptional repression. Different HDACs have distinct substrate specificities and functions in different biological processes. Accumulating evidence indicates that HDACs play a key role in the pathogenesis of multiple respiratory diseases.

Areas covered

After an extensive search of the PubMed database, Web of Science and ClinicalTrials.gov, covering the period from 1992 to 2024, this review summarizes recent advances in understanding the role of HDACs in inflammatory respiratory diseases, including allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma and chronic obstructive pulmonary disease (COPD). We also examine recent progress on the efficacy and potential use of histone deacetylase inhibitors (HDACi) for the treatment of these diseases.

Expert opinion

Available data indicate that HDACs play an important role in the development of common inflammatory respiratory diseases, and HDACi have shown promise as treatments for these diseases. However, the exact roles and underlying mechanisms of specific HDACs in disease pathogenesis require further study. Additional work is necessary to develop novel potent HDACi with high isoform selectivity.

KEYWORDS:

• Allergic rhinitis
• asthma
• chronic obstructive pulmonary disease
• chronic rhinosinusitis
• histone deacetylases
• histone deacetylase inhibitors

Article highlights

• Histone acetylation is a form of epigenetic regulation that dynamically regulates chromatin structure and gene expression through HDACs and HATs.

• HDACs have been shown to play important roles in the pathogenesis of various inflammatory respiratory diseases, such as AR, CRS, asthma, and COPD.

• Several types of HDACi have been shown to be effective at reducing airway inflammation, reversing airway remodeling, repairing the epithelial barrier, or reducing emphysema; therefore, HDACi may have therapeutic potential for treating inflammatory respiratory diseases.

• To date, most HDACi are still in the experimental stage, and further research is needed to determine their long-term safety and efficacy for the treatment of inflammatory respiratory diseases.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by grants from the National Key R&D Program of China [2022YFC2504100], the Program for Changjiang Scholars and Innovative Research Team (IRT13082), the Natural Science Foundation of Beijing [7212013 and 7222024], the National Natural Science Foundation of China [82171110], the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-022), the Beijing Municipal Science & Technology Commission [Z211100002921057], the Capital’s Funds for Health Improvement and Research [2022-1-1091], the Beijing New-star Plan of Science and Technology [20220484226 and 20230484476], and the Special Funds for the Construction of High-level Public Health Technical Talents (Lingjunrencai-01-08, Lingjunrencai-02-09).