Class IIa HDAC4 and HDAC7 Cooperatively Regulate Gene Transcription in Th17 Cell Differentiation

    April 2024 in “ Proceedings of the National Academy of Sciences ”
    Ka Lung Cheung, Li Zhao, Rajal Sharma, Anurupa Ghosh, Michael G. Appiah, Yifei Sun, Anbalagan Jaganathan, Yuan Hu, Alannah Lejeune, Feihong Xu, Xinye Han, Xueting Wang, Fan Zhang, Chunyan Ren, Martin J. Walsh, Huabao Xiong, Alexander M. Tsankov, Ming‐Ming Zhou
    TLDR HDAC4 and HDAC7 are crucial for Th17 cell development and could be targeted to treat inflammatory diseases.
    This study explores the roles of class IIa histone deacetylases, HDAC4 and HDAC7, in the differentiation of Th17 cells, which are linked to inflammatory diseases. HDAC4 promotes Th17-specific gene transcription, while HDAC7 represses negative regulators. The study shows that inhibiting these enzymes with TMP269 reduces Th17 cell differentiation and inflammation in a mouse model of colitis, suggesting that targeting HDAC4 and HDAC7 could be a therapeutic strategy for Th17-related inflammatory diseases. The findings emphasize the distinct yet cooperative roles of HDAC4 and HDAC7 in Th17 cell differentiation and their potential as therapeutic targets.
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