The regulation of Tfh cell differentiation by β-hydroxybutyrylation modification of transcription factor Bcl6.
The regulation of Tfh cell differentiation by β-hydroxybutyrylation modification of transcription factor Bcl6.
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DOI：
10.1007/s00412-023-00799-2
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发表时间：
2023-11
期刊：
影响因子：
1.6
通讯作者：
中科院分区：
文献类型：
--
作者：
转录抑制因子B细胞淋巴瘤6（Bcl 6）是参与Tfh细胞分化和生殖中心反应的主要转录因子，受多种生物学过程调控。然而，翻译后修饰，特别是赖氨酸β-羟基丁酰化（Kbhb）对Bcl 6的功能影响仍然难以捉摸。在这项研究中，我们发现Bcl 6被Kbhb修饰以影响Tfh细胞分化，导致细胞数量和细胞因子IL-21的减少。此外，通过质谱法从酶促反应中鉴定出修饰位点为位置376、377和379处的赖氨酸残基，这通过定点诱变和功能分析来证实。总的来说，我们目前的研究提供了证据的Bcl 6的Kbhb修饰，也产生了新的见解Tfh细胞分化的调节，这是一个起点，彻底了解的功能参与Kbhb修饰的Tfh和其他T细胞的分化。
Transcriptional repressor B cell lymphoma 6 (Bcl6) is a major transcription factor involved in Tfh cell differentiation and germinal center response, which is regulated by a variety of biological processes. However, the functional impact of post-translational modifications, particularly lysine β-hydroxybutyrylation (Kbhb), on Bcl6 remains elusive. In this study, we revealed that Bcl6 is modified by Kbhb to affect Tfh cell differentiation, resulting in the decrease of cell population and cytokine IL-21. Furthermore, the modification sites are identified from enzymatic reactions to be lysine residues at positions 376, 377, and 379 by mass spectrometry, which is confirmed by site-directed mutagenesis and functional analyses. Collectively, our present study provides evidence on the Kbhb modification of Bcl6 and also generates new insights into the regulation of Tfh cell differentiation, which is a starting point for a thorough understanding of the functional involvement of Kbhb modification in the differentiations of Tfh and other T cells.
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发表时间：
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