REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1653588
This article is part of the Research TopicAutoimmune Diseases: from molecular mechanisms to therapy developmentView all 22 articles
The regulatory mechanisms and treatment of HDAC6 in immune dysregulation diseases
Provisionally accepted
- Peking University First Hospital Taiyuan Hospital, Taiyuan, China
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Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc finger ubiquitin binding domain (ZnF-UBP). The deacetylation function of HDAC6 has been extensively studied with well-characterized substrates such as α-tubulin and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transport of aggregated proteins. subsequently, aggresomes is degraded by the autophagy-lysosome pathway. Additionally, Cells can utilize this HDAC6-dependent microtubule transport to assemble and activate inflammasomes, which play a critical role in immune regulation. HDAC6 displays a unique structure and cellular localization as well as diverse substrates, and exhibits a wider range of biological functions than other HDAC isoforms. HDAC6 has been intimately linked to a spectrum of diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriasis, neuritis, and the cancer immune microenvironment. This review systematically synthesizes the current research advancements of HDAC6, focusing on three key dimensions: the mechanism of action of HDAC6, therapeutic advancements, and translational prospects in clinical applications.
Keywords: HDAC6, cancer immunotherapy, Neuroinflammation, Autoimmune Diseases, Immunotherapy
Received: 25 Jun 2025; Accepted: 05 Sep 2025.
Copyright: © 2025 Liang, Wang, Xing, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kaiming Zhang, Peking University First Hospital Taiyuan Hospital, Taiyuan, China
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