小柯机器人

上海交通大学Ling-Yan Zheng等研究人员合作发现，赖氨酸乙酰转移酶6A通过对自身免疫中的葡萄糖代谢进行表观遗传学重编程，来维持CD4⁺ T细胞反应。2024年1月17日，《细胞—代谢》杂志在线发表了这项成果。

研究人员发现赖氨酸乙酰转移酶6A（KAT6A），这是一种临床上与自身免疫相关的表观遗传调控因子，它协调了CD4⁺ T细胞中葡萄糖的代谢重编程。体外促炎性CD4⁺ T细胞亚群的增殖和分化需要KAT6A，CD4⁺ T细胞缺乏KAT6A的小鼠对实验性自身免疫性脑脊髓炎和结肠炎的易感性较低。

从机理上讲，KAT6A可协调多个糖酵解基因所在染色质的组蛋白乙酰化丰度，从而影响葡萄糖代谢重编程和随后的CD4⁺ T细胞反应。在小鼠模型中使用KAT6A小分子抑制剂治疗显示，针对自身免疫中的KAT6A有很高的治疗价值。这项研究为免疫代谢的表观遗传编程提供了新的见解，并为自身免疫患者提出了潜在的治疗目标。

据悉，自身免疫中CD4⁺ T细胞反应增强的特点是广泛的代谢重编程。然而，驱动CD4⁺ T细胞代谢适应的表观遗传分子在很大程度上仍然未知。

附：英文原文

Title: Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity

Author: Jia-Yao Fu, Shi-Jia Huang, Bao-Li Wang, Jun-Hao Yin, Chang-Yu Chen, Jia-Bao Xu, Yan-Lin Chen, Shuo Xu, Ting Dong, Hao-Nan Zhou, Xin-Yi Ma, Yi-Ping Pu, Hui Li, Xiu-Juan Yang, Li-Song Xie, Zhi-Jun Wang, Qi Luo, Yan-Xiong Shao, Lei Ye, Zi-Rui Zong, Xin-Di Wei, Wan-Wen Xiao, Shu-Tong Niu, Yi-Ming Liu, He-Ping Xu, Chuang-Qi Yu, Sheng-Zhong Duan, Ling-Yan Zheng

Issue&Volume: 2024-01-17

Abstract: Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming.However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A),an epigenetic modulator that is clinically associated with autoimmunity, orchestratesthe metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatoryCD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis.Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatinwhere several glycolytic genes are located, thus affecting glucose metabolic reprogrammingand subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse modelsshows high therapeutic value for targeting KAT6A in autoimmunity. Our study providesnovel insights into the epigenetic programming of immunometabolism and suggests potentialtherapeutic targets for patients with autoimmunity.

DOI: 10.1016/j.cmet.2023.12.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00467-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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