睡眠剥夺免疫失调的细胞型特异性mRNA n6 -甲基腺苷格局及其调控机制

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Yakun Liu, Zhe Wang, Sha Liu, Xinrong Li, Denggao Wang, Dan Wang, Ying Li, Chaojie Liu, Yong Xu
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引用次数: 0

摘要

睡眠不足会损害白天的认知功能,是与免疫失调相关的各种疾病的危险因素。n6 -甲基腺苷(m6A)是一种常见的表观遗传RNA修饰,在调节神经发生和昼夜节律中起重要作用。m6A失调导致的免疫失衡已受到广泛关注。在这项研究中,我们通过RNA测序和单细胞转录组学数据集阐明了睡眠剥夺患者外周血中m6A调节因子的分布和具体机制。我们观察到m6A调节因子上调会加重睡眠缺失和免疫紊乱。女性对睡眠不足更敏感。值得注意的是,m6A调节因子ALKBH5在睡眠剥夺患者外周血单个核细胞(PBMC)中转录组水平下调。然而,ALKBH5在T细胞(TC)、B细胞(BC)和自然杀伤细胞(NK)中有细胞类型特异性上调,涉及通过异常的细胞间通讯介导不同细胞类型的配体-受体相互作用而获得性免疫机制的失调。此外,睡眠缺失的免疫失调可能通过SH-SY5Y和HT22细胞中ALKBH5和CD99之间的潜在途径进行调节。睡眠剥夺组CD3+/CD45+ T细胞ALKBH5 mRNA水平高于对照组。本研究表明,由m6A调节因子引起的异常m6A修饰模式在睡眠剥夺中先天免疫和获得性免疫失调中起关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cell-Type-Specific mRNA N6-Methyladenosine Landscape and Regulatory Mechanisms Underlying Immune Dysregulation of Sleep-Deprived

Sleep deprivation impairs daytime cognitive functioning and is a risk factor for various diseases related to immune dysregulation. N6-methyladenosine (m6A) is a common epigenetic RNA modification with essential roles in regulating neurogenesis and circadian rhythms. m6A dysregulation resulting in immune imbalance has received much attention. In this study, we elucidated the landscape and specific mechanisms of m6A regulators in the peripheral blood of patients with sleep deprivation through RNA sequencing and single-cell transcriptomics data sets. We observed that m6A regulator upregulation aggravated sleep loss and immune disorders. Women were more sensitive to sleep deprivation. Notably, m6A regulator ALKBH5 was downregulated in peripheral blood mononuclear cells (PBMC) of patients with sleep deprivation at the transcriptome level. However, ALKBH5 was cell-type specific upregulated in T cells (TC), B cells (BC), and natural killer (NK) cells, involving the dysregulation of acquired immune mechanisms by aberrant cell–cell communication that mediated ligand–receptor interactions across diverse cell types. Furthermore, the immune dysregulation of sleep loss could be regulated by a potential pathway between ALKBH5 and CD99 in SH-SY5Y and HT22 cells. Sleep deprivation group CD3+/CD45+ T cells had higher levels of ALKBH5 mRNA than the control group. This study demonstrated that abnormal m6A modification patterns caused by m6A regulators play a key role in the dysregulation of innate and acquired immunity in sleep deprivation.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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