Hdac10, histone deacetylase 10, is a class-IIb HDAC involved in various biological processes. It functions in epigenetic regulation by deacetylating substrates, which affects gene expression. It is associated with pathways such as those related to macrophage polarization, autophagy, and immune responses, and is of significance in multiple diseases [1,2,3,5,7]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In KO mouse models, Hdac10 deficiency protected mice from airway inflammation in an experimental asthma model as it attenuated STAT3 expression and decreased M2 macrophage polarization [1]. In melanoma cells, depletion of Hdac10 upregulated SPARC expression, repressing cell growth and BRAF inhibitor resistance [2,6]. In murine Tregs, Hdac10 deletion led to increased suppressive function both in vitro and in vivo, protecting mice from colitis and promoting long-term allograft survival in cardiac transplants [3]. In KRAS-driven lung adenocarcinoma mouse models, Hdac10 deletion accelerated tumor development, increased macrophage infiltration, and shortened survival time [4].

In conclusion, Hdac10 plays crucial roles in processes like macrophage M2 polarization, melanoma cell growth regulation, T-regulatory cell function, and lung carcinogenesis. Studies using KO/CKO mouse models have provided insights into its role in diseases such as asthma, melanoma, inflammatory disorders, and lung cancer, highlighting its potential as a therapeutic target in these disease areas [1,2,3,4].

References:

1. Zhong, Yu, Huang, Tong, Huang, Jiewen, Tang, Jing, Lai, Tianwen. 2023. The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation. In Theranostics, 13, 3568-3581. doi:10.7150/thno.82535. https://pubmed.ncbi.nlm.nih.gov/37441601/

2. Ling, Hongbo, Li, Yixuan, Peng, Changmin, Yang, Shengyu, Seto, Edward. 2024. HDAC10 inhibition represses melanoma cell growth and BRAF inhibitor resistance via upregulating SPARC expression. In NAR cancer, 6, zcae018. doi:10.1093/narcan/zcae018. https://pubmed.ncbi.nlm.nih.gov/38650694/

3. Dahiya, Satinder, Beier, Ulf H, Wang, Liqing, Wallace, Douglas C, Hancock, Wayne W. 2020. HDAC10 deletion promotes Foxp3+ T-regulatory cell function. In Scientific reports, 10, 424. doi:10.1038/s41598-019-57294-x. https://pubmed.ncbi.nlm.nih.gov/31949209/

4. Li, Yixuan, Zhang, Xiangyang, Zhu, Shaoqi, Sepulveda, Antonia, Seto, Edward. 2020. HDAC10 Regulates Cancer Stem-Like Cell Properties in KRAS-Driven Lung Adenocarcinoma. In Cancer research, 80, 3265-3278. doi:10.1158/0008-5472.CAN-19-3613. https://pubmed.ncbi.nlm.nih.gov/32540961/

5. Shinsky, Stephen A, Christianson, David W. 2018. Polyamine Deacetylase Structure and Catalysis: Prokaryotic Acetylpolyamine Amidohydrolase and Eukaryotic HDAC10. In Biochemistry, 57, 3105-3114. doi:10.1021/acs.biochem.8b00079. https://pubmed.ncbi.nlm.nih.gov/29533602/

6. Ling, Hongbo, Li, Yixuan, Peng, Changmin, Yang, Shengyu, Seto, Edward. 2023. HDAC10 blockade upregulates SPARC expression thereby repressing melanoma cell growth and BRAF inhibitor resistance. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.12.05.570182. https://pubmed.ncbi.nlm.nih.gov/38106051/

7. Zhou, Wenkai, Wang, Jiaming, Wang, Xin, Jiang, Minghong, Cao, Xuetao. 2022. Degradation of HDAC10 by autophagy promotes IRF3-mediated antiviral innate immune responses. In Science signaling, 15, eabo4356. doi:10.1126/scisignal.abo4356. https://pubmed.ncbi.nlm.nih.gov/36538592/