{"title":"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","authors":"Yakun Liu, Zhe Wang, Sha Liu, Xinrong Li, Denggao Wang, Dan Wang, Ying Li, Chaojie Liu, Yong Xu","doi":"10.1111/jpi.70046","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Sleep deprivation impairs daytime cognitive functioning and is a risk factor for various diseases related to immune dysregulation. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is a common epigenetic RNA modification with essential roles in regulating neurogenesis and circadian rhythms. m<sup>6</sup>A dysregulation resulting in immune imbalance has received much attention. In this study, we elucidated the landscape and specific mechanisms of m<sup>6</sup>A regulators in the peripheral blood of patients with sleep deprivation through RNA sequencing and single-cell transcriptomics data sets. We observed that m<sup>6</sup>A regulator upregulation aggravated sleep loss and immune disorders. Women were more sensitive to sleep deprivation. Notably, m<sup>6</sup>A regulator <i>ALKBH5</i> was downregulated in peripheral blood mononuclear cells (PBMC) of patients with sleep deprivation at the transcriptome level. However, <i>ALKBH5</i> 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<sup>+</sup>/CD45<sup>+</sup> T cells had higher levels of <i>ALKBH5</i> mRNA than the control group. This study demonstrated that abnormal m<sup>6</sup>A modification patterns caused by m<sup>6</sup>A regulators play a key role in the dysregulation of innate and acquired immunity in sleep deprivation.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cell-Type-Specific mRNA N6-Methyladenosine Landscape and Regulatory Mechanisms Underlying Immune Dysregulation of Sleep-Deprived\",\"authors\":\"Yakun Liu, Zhe Wang, Sha Liu, Xinrong Li, Denggao Wang, Dan Wang, Ying Li, Chaojie Liu, Yong Xu\",\"doi\":\"10.1111/jpi.70046\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Sleep deprivation impairs daytime cognitive functioning and is a risk factor for various diseases related to immune dysregulation. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is a common epigenetic RNA modification with essential roles in regulating neurogenesis and circadian rhythms. m<sup>6</sup>A dysregulation resulting in immune imbalance has received much attention. In this study, we elucidated the landscape and specific mechanisms of m<sup>6</sup>A regulators in the peripheral blood of patients with sleep deprivation through RNA sequencing and single-cell transcriptomics data sets. We observed that m<sup>6</sup>A regulator upregulation aggravated sleep loss and immune disorders. Women were more sensitive to sleep deprivation. Notably, m<sup>6</sup>A regulator <i>ALKBH5</i> was downregulated in peripheral blood mononuclear cells (PBMC) of patients with sleep deprivation at the transcriptome level. However, <i>ALKBH5</i> 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<sup>+</sup>/CD45<sup>+</sup> T cells had higher levels of <i>ALKBH5</i> mRNA than the control group. This study demonstrated that abnormal m<sup>6</sup>A modification patterns caused by m<sup>6</sup>A regulators play a key role in the dysregulation of innate and acquired immunity in sleep deprivation.</p></div>\",\"PeriodicalId\":198,\"journal\":{\"name\":\"Journal of Pineal Research\",\"volume\":\"77 3\",\"pages\":\"\"},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2025-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pineal Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jpi.70046\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pineal Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jpi.70046","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.