The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

Frontiers in Immunology

Hao Li¹  Yongqing Li²  Hui Hu³  Panpan Chang⁴  Tianbing Wang⁴ 

[1] Department of Emergency, First Hospital of China Medical University, Shenyang, China;Department of Surgery, University of Michigan, Ann Arbor, MI, United States;Department of Traumatology, Central Hospital of Chongqing University, Chongqing Emergency Medical Center, Chongqing, China;Trauma Medicine Center, Peking University People’s Hospital, Key Laboratory of Trauma and Neural Regeneration (Peking University), National Center for Trauma Medicine of China, Beijing, China;

关键词: HDAC6;    autophagy;    NLRP3 inflammasome;    inflammation;    post-translational modification;   

DOI  :  10.3389/fimmu.2021.763831

来源: DOAJ

【 摘 要 】

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

【 授权许可】

Unknown