Zhao Xinyu, Qiao Xue, Yu Simiao, Jin Yuhao, Niu Jixiang, Li Jie, Xu Yingmei, Yang Yuehong, Wang Lingling, Song Linsheng
College of Life Sciences, Liaoning Normal University, Dalian 116029, China.
Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian 116023, China.
Int J Mol Sci. 2024 Dec 7;25(23):13174. doi: 10.3390/ijms252313174.
Immune priming confers a sustained, augmented response of innate immune cells to a secondary challenge, a process that is characteristically reliant on metabolic reprogramming. Recent evidence suggests that histone demethylases play essential roles in the immune priming, while its regulation role in the metabolic reprogramming remains largely unknown. In the present study, the concentration of glucose was significantly down-regulated in the hemocytes of crab after secondary stimulation with , while the expression levels of phosphofructokinase (PFK) pyruvate kinase (PK), hexokinase-2 (HK-2) and Glucose-6-phosphate dehydrogenase (G-6-PD), along with the concentrations of lactate and the ratio of NAD/NADH, were elevated. Additionally, the levels of H3K9me3 and its enrichment at the promoters of PFK and G-6-PD were significantly decreased at 7 days after stimulation. The lysine Demethylase 4 homologue (KDM4) was observed to translocate into the nucleus of crab hemocytes after stimulation, and its activity markedly increased after secondary stimulation with . Following RNA interference of KDM4, there was a significant increase in H3K9me3 levels, and the enrichment of H3K9me3 at the PFK and G-6-PD promoters, as well as the concentration of glucose, in the hemocytes of crabs after secondary stimulation with . Furthermore, mRNA transcripts of PFK and G-6-PD, as well as the concentration of lactate and ratio of NAD/NADH, significantly decreased after secondary stimulation. These results suggested that KDM4 mediates the enrichment of H3K9me3 at the promoters of PFK and G-6-PD, thereby regulating glycolysis during the immune priming of crabs.
免疫致敏赋予先天免疫细胞对二次刺激产生持续增强的反应，这一过程通常依赖于代谢重编程。最近的证据表明，组蛋白去甲基化酶在免疫致敏中起重要作用，而其在代谢重编程中的调节作用仍 largely 未知。在本研究中，用 二次刺激后，蟹血细胞中的葡萄糖浓度显著下调，而磷酸果糖激酶（PFK）、丙酮酸激酶（PK）、己糖激酶 -2（HK -2）和葡萄糖 -6 -磷酸脱氢酶（G -6 -PD）的表达水平，以及乳酸浓度和 NAD/NADH 比值均升高。此外，用 刺激 7 天后，H3K9me3 的水平及其在 PFK 和 G -6 -PD 启动子处的富集显著降低。观察到赖氨酸去甲基化酶 4 同源物（KDM4）在用 刺激后易位到蟹血细胞的细胞核中，并且在用 二次刺激后其活性显著增加。在对 KDM4 进行 RNA 干扰后，用 二次刺激后蟹血细胞中 H3K9me3 水平显著增加，H3K9me3 在 PFK 和 G -6 -PD 启动子处的富集以及葡萄糖浓度也显著增加。此外，二次刺激后 PFK 和 G -6 -PD 的 mRNA 转录本以及乳酸浓度和 NAD/NADH 比值显著降低。这些结果表明，KDM4 介导 H3K9me3 在 PFK 和 G -6 -PD 启动子处的富集，从而在蟹的免疫致敏过程中调节糖酵解。
