Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
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DOI：
10.3390/ijms24032010
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发表时间：
2023-01-19
影响因子：
5.6
通讯作者：
Hanson, Maureen R.
中科院分区：
文献类型：
--
作者：
Maya, Jessica;Leddy, Sabrina M.;Gottschalk, C. Gunnar;Peterson, Daniel L.;Hanson, Maureen R.
关键词：
肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种致残的多系统疾病，患者患有疲劳、炎症症状、认知功能障碍和标志性症状--劳后不适。虽然这种疾病的病因尚不清楚，但有证据表明，除了患者的症状和常见的疾病症状外，还有一种潜在的感染性成分，涉及免疫系统功能障碍。为了进一步了解ME/CFS淋巴细胞的状态，我们通过对脂肪酸氧化的隐含扰动，表征了循环中和过夜刺激后分离的自然杀伤细胞、CD4+T细胞和CD8+T细胞中脂肪酸的作用。我们在各种实验中检查了从至少8名和多达20名受试者获得的免疫细胞脂肪酸特征的样本，发现所有三种分离的细胞类型都增加了ME/CFS样本对脂质的利用和参与这一代谢途径的相关蛋白质水平，特别是在更高的能量需求和激活期间。在T细胞中，我们描述了导致这些代谢转变的细胞群，包括CD4+记忆细胞、CD4+效应细胞、CD8+幼稚细胞和CD8+记忆细胞。我们还发现，ME/CFS患者和健康对照样本的CD4+T细胞脂肪酸代谢测量与人口学数据之间存在显著的相关性。这些发现为ME/CFS免疫细胞代谢功能障碍提供了支持。我们进一步假设这些改变的燃料依赖可能对T和NK细胞效应器功能产生影响，这可能有助于阐明疾病的作用机制。
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While the cause of this disease remains unknown, there is evidence of a potential infectious component that, along with patient symptoms and common onsets of the disease, implicates immune system dysfunction. To further our understanding of the state of ME/CFS lymphocytes, we characterized the role of fatty acids in isolated Natural Killer cells, CD4+ T cells, and CD8+ T cells in circulation and after overnight stimulation, through implicit perturbations to fatty acid oxidation. We examined samples obtained from at least 8 and as many as 20 subjects for immune cell fatty acid characterization in a variety of experiments and found that all three isolated cell types increased their utilization of lipids and levels of pertinent proteins involved in this metabolic pathway in ME/CFS samples, particularly during higher energy demands and activation. In T cells, we characterized the cell populations contributing to these metabolic shifts, which included CD4+ memory cells, CD4+ effector cells, CD8+ naïve cells, and CD8+ memory cells. We also discovered that patients with ME/CFS and healthy control samples had significant correlations between measurements of CD4+ T cell fatty acid metabolism and demographic data. These findings provide support for metabolic dysfunction in ME/CFS immune cells. We further hypothesize about the consequences that these altered fuel dependencies may have on T and NK cell effector function, which may shed light on the illness’s mechanism of action.
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影响因子：
8.8
作者：
Ecker C;Guo L;Voicu S;Gil-de-Gómez L;Medvec A;Cortina L;Pajda J;Andolina M;Torres-Castillo M;Donato JL;Mansour S;Zynda ER;Lin PY;Varela-Rohena A;Blair IA;Riley JL
通讯作者：
Riley JL
DOI：
10.1172/jci148546
发表时间：
2022-01-04
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Corrado M;Pearce EL
通讯作者：
Pearce EL
影响因子：
7.3
作者：
Gardiner CM;Finlay DK
通讯作者：
Finlay DK
影响因子：
4.7
作者：
通讯作者：
--
影响因子：
4.4
作者：
Brenu, Ekua Weba;Huth, Teilah K.;Marshall-Gradisnik, Sonya M.
通讯作者：
Marshall-Gradisnik, Sonya M.