{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:56:56Z","timestamp":1791619016255,"version":"4.3.4"},"reference-count":145,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWOTM1249"],"award-info":[{"award-number":["FWOTM1249"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWOTM1051"],"award-info":[{"award-number":["FWOTM1051"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWOTM1069"],"award-info":[{"award-number":["FWOTM1069"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["SCO36942"],"award-info":[{"award-number":["SCO36942"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001981","name":"ME Research UK","doi-asserted-by":"publisher","award":["FWOTM1249"],"award-info":[{"award-number":["FWOTM1249"]}],"id":[{"id":"10.13039\/501100001981","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001981","name":"ME Research UK","doi-asserted-by":"publisher","award":["FWOTM1051"],"award-info":[{"award-number":["FWOTM1051"]}],"id":[{"id":"10.13039\/501100001981","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001981","name":"ME Research UK","doi-asserted-by":"publisher","award":["FWOTM1069"],"award-info":[{"award-number":["FWOTM1069"]}],"id":[{"id":"10.13039\/501100001981","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001981","name":"ME Research UK","doi-asserted-by":"publisher","award":["SCO36942"],"award-info":[{"award-number":["SCO36942"]}],"id":[{"id":"10.13039\/501100001981","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients\u2019 quality of life. Despite its impact, no curative treatments exist, largely due to the limited understanding of the disease\u2019s underlying pathophysiology. Mitochondrial dysfunction, leading to impaired energy production and utilization, is believed to play a key role in the onset of fatigue and PEM, positioning it as a potential key pathophysiological mechanism underlying ME\/CFS. Additionally, the disorder shows similarities to chronic viral infections, with frequent reports of immune system alterations, suggesting a critical role for immune (dys)functioning. In particular, the roles of immune senescence and immune exhaustion\u2014two fundamental immune states\u2014remain poorly understood in ME\/CFS. This state-of-the-art review explores how metabolic dysfunction and immune dysfunction may be interconnected in ME\/CFS, proposing that energy deficits may directly impair immune function. By examining this metabolic\u2013immune interplay, this review highlights potential pathways for developing innovative therapeutic strategies that target both energy metabolism and immune regulation, offering hope for improving patient outcomes.<\/jats:p>","DOI":"10.3390\/biom15030357","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T07:37:17Z","timestamp":1740987437000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Unravelling the Connection Between Energy Metabolism and Immune Senescence\/Exhaustion in Patients with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5996-031X","authenticated-orcid":false,"given":"Jente","family":"Van Campenhout","sequence":"first","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1308-6171","authenticated-orcid":false,"given":"Yanthe","family":"Buntinx","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-3124","authenticated-orcid":false,"given":"Huan-Yu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Flanders Research Foundation-FWO, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-6632","authenticated-orcid":false,"given":"Arne","family":"Wyns","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Kapucijnenvoer 35, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-2217","authenticated-orcid":false,"given":"Andrea","family":"Polli","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Flanders Research Foundation-FWO, 1090 Brussels, Belgium"},{"name":"Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Kapucijnenvoer 35, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4976-6563","authenticated-orcid":false,"given":"Jo","family":"Nijs","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Unit of Physiotherapy, Department of Health and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"},{"name":"Department of Physical Medicine and Physiotherapy, University Hospital Brussels, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-3696","authenticated-orcid":false,"given":"Joeri L.","family":"Aerts","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro-Aging & Viro-Immunotherapy, Center for Neurosciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-5663","authenticated-orcid":false,"given":"Thessa","family":"Laeremans","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro-Aging & Viro-Immunotherapy, Center for Neurosciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-5636","authenticated-orcid":false,"given":"Jolien","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Flanders Research Foundation-FWO, 1090 Brussels, Belgium"},{"name":"Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Kapucijnenvoer 35, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.clinthera.2018.12.016","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences","volume":"41","author":"Natelson","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e113629","DOI":"10.5812\/aapm.113629","article-title":"A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome","volume":"11","author":"Noor","year":"2021","journal-title":"Anesth. Pain. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rivera, M.C., Mastronardi, C., Silva-Aldana, C.T., Arcos-Burgos, M., and Lidbury, B.A. (2019). Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030091"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12967-020-02455-0","article-title":"Review of Case Definitions for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)","volume":"18","author":"Lim","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_5","first-page":"208","article-title":"Mitochondrial Dysfunction and the Pathophysiology of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)","volume":"5","author":"Booth","year":"2012","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bbacli.2014.04.001","article-title":"Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature","volume":"1","author":"Filler","year":"2014","journal-title":"BBA Clin."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"McGregor, N.R., Armstrong, C.W., Lewis, D.P., and Gooley, P.R. (2019). Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME\/CFS Cases. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030070"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Missailidis, D., Annesley, S.J., Allan, C.Y., Sanislav, O., Lidbury, B.A., Lewis, D.P., and Fisher, P.R. (2020). An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME\/CFS Patients. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints201909.0043.v2"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12967-020-02452-3","article-title":"A Systematic Review of Mitochondrial Abnormalities in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome\/Systemic Exertion Intolerance Disease","volume":"18","author":"Holden","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tomas, C., Brown, A., Strassheim, V., Elson, J., Newton, J., and Manning, P. (2017). Cellular Bioenergetics Is Impaired in Patients with Chronic Fatigue Syndrome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186802"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tomas, C., Elson, J.L., Strassheim, V., Newton, J.L., and Walker, M. (2020). The Effect of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) Severity on Cellular Bioenergetic Function. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231136"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e14138","DOI":"10.14814\/phy2.14138","article-title":"Abnormal Blood Lactate Accumulation during Repeated Exercise Testing in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"7","author":"Lien","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1080\/17513758.2012.704083","article-title":"Can Persistent Epstein-Barr Virus Infection Induce Chronic Fatigue Syndrome as a Pavlov Reflex of the Immune Response?","volume":"6","author":"Agliari","year":"2012","journal-title":"J. Biol. Dyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1093\/clinids\/18.Supplement_1.S117","article-title":"Viral Studies of Chronic Fatigue Syndrome","volume":"18","author":"Levy","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri2959","article-title":"Are Senescence and Exhaustion Intertwined or Unrelated Processes That Compromise Immunity?","volume":"11","author":"Akbar","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rigoulet, M., Bouchez, C.L., Paumard, P., Ransac, S., Cuvellier, S., Duvezin-Caubet, S., Mazat, J.P., and Devin, A. (2020). Cell Energy Metabolism: An Update. Biochim. Biophys. Acta Bioenerg., 1861.","DOI":"10.1016\/j.bbabio.2020.148276"},{"key":"ref_17","unstructured":"Chandel, N. (2015). Navigating Metabolism, Cold Spring Harbor Laboratory Press."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C377","DOI":"10.1152\/ajpcell.1990.258.3.C377","article-title":"Regulation of Oxidative Phosphorylation in the Mammalian Cell","volume":"258","author":"Balaban","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.cell.2006.06.010","article-title":"Mitochondria: Dynamic Organelles in Disease, Aging, and Development","volume":"125","author":"Chan","year":"2006","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cvsm.2007.10.004","article-title":"Mitochondrial Pathophysiology, Reactive Oxygen Species, and Cardiovascular Diseases","volume":"38","author":"Gao","year":"2008","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41568-021-00435-0","article-title":"The Role of ROS in Tumour Development and Progression","volume":"22","author":"Cheung","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bbagen.2013.10.041","article-title":"Mitochondrial Quality Control and Communications with the Nucleus Are Important in Maintaining Mitochondrial Function and Cell Health","volume":"1840","author":"Kotiadis","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Theurey, P., and Pizzo, P. (2018). The Aging Mitochondria. Genes, 9.","DOI":"10.3390\/genes9010022"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.yexmp.2006.09.008","article-title":"Mitochondrial Dysfunction and Molecular Pathways of Disease","volume":"83","author":"Pieczenik","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Luo, Y., Ma, J., and Lu, W. (2020). The Significance of Mitochondrial Dysfunction in Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165598"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1177\/1535370216641787","article-title":"Role of Mitochondrial Dysfunction in Cancer Progression","volume":"241","author":"Hsu","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fernandez-Guerra, P., Gonzalez-Ebsen, A.C., Boonen, S.E., Courraud, J., Gregersen, N., Mehlsen, J., Palmfeldt, J., Olsen, R.K.J., and Brinth, L.S. (2021). Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules, 11.","DOI":"10.3390\/biom11070961"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1479-5876-8-93","article-title":"Patients with Chronic Fatigue Syndrome Performed Worse than Controls in a Controlled Repeated Exercise Study despite a Normal Oxidative Phosphorylation Capacity","volume":"8","author":"Vermeulen","year":"2010","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e6500","DOI":"10.7717\/peerj.6500","article-title":"Mitochondrial Complex Activity in Permeabilised Cells of Chronic Fatigue Syndrome Patients Using Two Cell Types","volume":"7","author":"Tomas","year":"2019","journal-title":"PeerJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1517\/14728222.2013.818657","article-title":"The Role of Mitochondrial Dysfunctions Due to Oxidative and Nitrosative Stress in the Chronic Pain or Chronic Fatigue Syndromes and Fibromyalgia Patients: Peripheral and Central Mechanisms as Therapeutic Targets?","volume":"17","author":"Meeus","year":"2013","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_31","first-page":"14","article-title":"Role of Mitochondria, Oxidative Stress and the Response to Antioxidants in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Possible Approach to SARS-CoV-2 \u201cLong-Haulers\u201d?","volume":"7","author":"Wood","year":"2021","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2024358118","DOI":"10.1073\/pnas.2024358118","article-title":"Redox Imbalance Links COVID-19 and Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"118","author":"Paul","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s12967-020-02341-9","article-title":"Altered Muscle Membrane Potential and Redox Status Differentiates Two Subgroups of Patients with Chronic Fatigue Syndrome","volume":"18","author":"Jammes","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1007\/s11306-015-0816-5","article-title":"Metabolic Profiling Reveals Anomalous Energy Metabolism and Oxidative Stress Pathways in Chronic Fatigue Syndrome Patients","volume":"11","author":"Armstrong","year":"2015","journal-title":"Metabolomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1186\/s12967-020-02533-3","article-title":"A SWATH-MS Analysis of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Peripheral Blood Mononuclear Cell Proteomes Reveals Mitochondrial Dysfunction","volume":"18","author":"Sweetman","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR Signaling in Growth and Metabolism","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"ref_37","first-page":"1","article-title":"Chronic Fatigue Syndrome and Mitochondrial Dysfunction","volume":"2","author":"Myhill","year":"2009","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_38","first-page":"74","article-title":"Analyzing Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis: Potential Role of L-Carnitine","volume":"13","author":"Modanloo","year":"2019","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_39","first-page":"470","article-title":"Coenzyme Q10 Deficiency in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) Is Related to Fatigue, Autonomic and Neurocognitive Symptoms and Is Another Risk Factor Explaining the Early Mortality in ME\/CFS Due to Cardiovascular Disorder","volume":"30","author":"Maes","year":"2009","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1089\/ars.2022.0018","article-title":"Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome?","volume":"36","author":"Domingo","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Castro-Marrero, J., Segundo, M.J., Lacasa, M., Martinez-Martinez, A., Senta\u00f1es, R.S., and Alegre-Martin, J. (2021). Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 13.","DOI":"10.3390\/nu13082658"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s12035-013-8477-8","article-title":"Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications","volume":"48","author":"Morris","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e89376","DOI":"10.1172\/jci.insight.89376","article-title":"Metabolic Profiling Indicates Impaired Pyruvate Dehydrogenase Function in Myalgic Encephalopathy\/Chronic Fatigue Syndrome","volume":"1","author":"Fluge","year":"2016","journal-title":"JCI Insight"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e157621","DOI":"10.1172\/jci.insight.157621","article-title":"Plasma Metabolomics Reveals Disrupted Response and Recovery Following Maximal Exercise in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"7","author":"Germain","year":"2022","journal-title":"JCI Insight"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Theoharides, T.C., Tsilioni, I., and Natelson, B. (2021). Exosome-Associated Mitochondrial DNA Is Elevated in Patients with ME\/CFS and Stimulates Human Cultured Microglia to Secrete IL-1\u03b2. Preprint.","DOI":"10.21203\/rs.3.rs-154011\/v1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1111\/ejn.15828","article-title":"Exosome-Associated Mitochondrial DNA from Patients with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Stimulates Human Microglia to Release IL-1\u03b2","volume":"56","author":"Tsilioni","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12967-016-0771-6","article-title":"Mitochondrial DNA Variants Correlate with Symptoms in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"14","author":"Germain","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Venter, M., Tomas, C., Pienaar, I.S., Strassheim, V., Erasmus, E., Ng, W.F., Howell, N., Newton, J.L., Van der Westhuizen, F.H., and Elson, J.L. (2019). MtDNA Population Variation in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome in Two Populations: A Study of Mildly Deleterious Variants. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-39060-1"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Trivedi, M.S., Oltra, E., Sarria, L., Rose, N., Beljanski, V., Fletcher, M.A., Klimas, N.G., and Nathanson, L. (2018). Identification of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome-Associated DNA Methylation Patterns. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201066"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13148-020-00960-z","article-title":"Changes in DNA Methylation Profiles of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Patients Reflect Systemic Dysfunctions","volume":"12","author":"Helliwell","year":"2020","journal-title":"Clin. Epigenetics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13148-020-00976-5","article-title":"Mitochondrial Metabolism and DNA Methylation: A Review of the Interaction between Two Genomes","volume":"12","author":"Lopes","year":"2020","journal-title":"Clin. Epigenetics"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tzika, E., Dreker, T., and Imhof, A. (2018). Epigenetics and Metabolism in Health and Disease. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00361"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the Immune Response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"150923","DOI":"10.1016\/j.soncn.2019.08.002","article-title":"Cancer and the Immune System: The History and Background of Immunotherapy","volume":"35","author":"Abbott","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s12974-022-02605-9","article-title":"The Role of the Adaptive Immune System and T Cell Dysfunction in Neurodegenerative Diseases","volume":"19","author":"DeMaio","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cliff, J.M., King, E.C., Lee, J.S., Sep\u00falveda, N., Wolf, A.S., Kingdon, C., Bowman, E., Dockrell, H.M., Nacul, L., and Lacerda, E. (2019). Cellular Immune Function in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00796"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12967-023-03887-0","article-title":"The Persistent Viral Infections in the Development and Severity of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"21","author":"Krumina","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/cei.12043","article-title":"Altered Functional B Cell Subset Populations in Patients with Chronic Fatigue Syndrome Compared to Healthy Controls","volume":"172","author":"Bradley","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1172\/JCI132185","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Patients Exhibit Altered T Cell Metabolism and Cytokine Associations","volume":"130","author":"Mandarano","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_60","first-page":"1013","article-title":"Impairments of the 2-5A Synthetase\/RNase L Pathway in Chronic Fatigue Syndrome","volume":"19","author":"Nijs","year":"2005","journal-title":"In Vivo"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s13643-019-1202-6","article-title":"A Systematic Review of Natural Killer Cells Profile and Cytotoxic Function in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"8","author":"Cabanas","year":"2019","journal-title":"Syst. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Corbitt, M., Eaton-Fitch, N., Staines, D., Cabanas, H., and Marshall-Gradisnik, S. (2019). A Systematic Review of Cytokines in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis\/Systemic Exertion Intolerance Disease (CFS\/ME\/SEID). BMC Neurol., 19.","DOI":"10.1186\/s12883-019-1433-0"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.autrev.2008.08.003","article-title":"Immunological Aspects of Chronic Fatigue Syndrome","volume":"8","author":"Lorusso","year":"2009","journal-title":"Autoimmun. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, Cellular Senescence, and Cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molcel.2009.09.021","article-title":"Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence","volume":"36","author":"Adams","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular Senescence: When Bad Things Happen to Good Cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.18632\/aging.101617","article-title":"The Senescent Cell Epigenome","volume":"10","author":"Yang","year":"2018","journal-title":"Aging"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression","volume":"5","author":"Desprez","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/ni.2588","article-title":"Understanding Immunosenescence to Improve Responses to Vaccines","volume":"14","author":"Goronzy","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.biopsych.2016.07.008","article-title":"Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women\u2019s Health Initiative Study","volume":"81","author":"Carroll","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e2202780119","DOI":"10.1073\/pnas.2202780119","article-title":"Social Stressors Associated with Age-Related T Lymphocyte Percentages in Older US Adults: Evidence from the US Health and Retirement Study","volume":"119","author":"Klopack","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.coi.2012.12.003","article-title":"T Cell Anergy, Exhaustion, Senescence, and Stemness in the Tumor Microenvironment","volume":"25","author":"Crespo","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition","volume":"31","author":"Long","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41590-020-0643-3","article-title":"Sestrins Induce Natural Killer Function in Senescent-like CD8+ T Cells","volume":"21","author":"Pereira","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"112236","DOI":"10.1016\/j.celrep.2023.112236","article-title":"KIR+CD8+ and NKG2A+CD8+ T Cells Are Distinct Innate-like Populations in Humans","volume":"42","author":"Choi","year":"2023","journal-title":"Cell Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S0531-5565(03)00160-8","article-title":"Marked Increase with Age of Type 1 Cytokines within Memory and Effector\/Cytotoxic CD8+ T Cells in Humans: A Contribution to Understand the Relationship between Inflammation and Immunosenescence","volume":"38","author":"Zanni","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1006\/clim.2000.4894","article-title":"The Increase of IFN-Gamma Production through Aging Correlates with the Expanded CD8(+high)CD28(-)CD57(+) Subpopulation","volume":"96","author":"Merino","year":"2000","journal-title":"Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular Senescence: The Good, the Bad and the Unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/acel.12055","article-title":"In Senescence, Age-Associated B Cells Secrete TNF\u03b1 and Inhibit Survival of B-Cell Precursors","volume":"12","author":"Ratliff","year":"2013","journal-title":"Aging Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exger.2014.01.004","article-title":"High TNF-\u03b1 Levels in Resting B Cells Negatively Correlate with Their Response","volume":"54","author":"Frasca","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.arr.2010.12.002","article-title":"B Cells and Immunosenescence: A Focus on IgG+IgD-CD27- (DN) B Cells in Aged Humans","volume":"10","author":"Bulati","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7871814","DOI":"10.1155\/2018\/7871814","article-title":"Effect of Aging on NK Cell Population and Their Proliferation at Ex Vivo Culture Condition","volume":"2018","author":"Gounder","year":"2018","journal-title":"Anal. Cell. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Streltsova, M.A., Erokhina, S.A., Kanevskiy, L.M., Lee, D.A., Telford, W.G., Sapozhnikov, A.M., and Kovalenko, E.I. (2018). Analysis of NK Cell Clones Obtained Using Interleukin-2 and Gene-Modified K562 Cells Revealed the Ability of \u201cSenescent\u201d NK Cells to Lose CD57 Expression and Start Expressing NKG2A. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208469"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1182\/blood-2010-04-281675","article-title":"Expression Patterns of NKG2A, KIR, and CD57 Define a Process of CD56dim NK-Cell Differentiation Uncoupled from NK-Cell Education","volume":"116","author":"Riese","year":"2010","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1182\/blood-2002-02-0657","article-title":"Lack of Proliferative Capacity of Human Effector and Memory T Cells Expressing Killer Cell Lectinlike Receptor G1 (KLRG1)","volume":"100","author":"Voehringer","year":"2002","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12967-018-1414-x","article-title":"Association of Chronic Fatigue Syndrome with Premature Telomere Attrition","volume":"16","author":"Rajeevan","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1479-5876-7-96","article-title":"Plasma Cytokines in Women with Chronic Fatigue Syndrome","volume":"7","author":"Fletcher","year":"2009","journal-title":"J. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"103267","DOI":"10.1016\/j.jaut.2024.103267","article-title":"Diverse Immunological Dysregulation, Chronic Inflammation, and Impaired Erythropoiesis in Long COVID Patients with Chronic Fatigue Syndrome","volume":"147","author":"Saito","year":"2024","journal-title":"J. Autoimmun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1479-5876-9-81","article-title":"Immunological Abnormalities as Potential Biomarkers in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis","volume":"9","author":"Brenu","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"764","DOI":"10.7150\/ijms.12399","article-title":"Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis Patients","volume":"12","author":"Hardcastle","year":"2015","journal-title":"Int. J. Med. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s00421-014-2910-1","article-title":"Dimensions of Pure Chronic Fatigue: Psychophysical, Cognitive and Biological Correlates in the Chronic Fatigue Syndrome","volume":"114","author":"Neu","year":"2014","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"E7150","DOI":"10.1073\/pnas.1710519114","article-title":"Cytokine Signature Associated with Disease Severity in Chronic Fatigue Syndrome Patients","volume":"114","author":"Montoya","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1007\/s12035-019-1549-7","article-title":"Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome","volume":"56","author":"Espinosa","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Hardcastle, S.L., Brenu, E.W., Johnston, S., Nguyen, T., Huth, T., Wong, N., Ramos, S., Staines, D., and Marshall-Gradisnik, S. (2015). Characterisation of Cell Functions and Receptors in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis (CFS\/ME). BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0101-4"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1479-5876-11-68","article-title":"Screening NK-, B- and T-Cell Phenotype and Function in Patients Suffering from Chronic Fatigue Syndrome","volume":"11","author":"Curriu","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Rivas, J.L., Palencia, T., Fern\u00e1ndez, G., and Garc\u00eda, M. (2018). Association of T and NK Cell Phenotype With the Diagnosis of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01028"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-3083.1991.tb01777.x","article-title":"A Comprehensive Immunological Analysis in Chronic Fatigue Syndrome","volume":"33","author":"Gupta","year":"1991","journal-title":"Scand. J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s12967-018-1696-z","article-title":"Evaluation of Four Clinical Laboratory Parameters for the Diagnosis of Myalgic Encephalomyelitis","volume":"16","author":"Mijatovic","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/cei.12749","article-title":"Extended B Cell Phenotype in Patients with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Cross-Sectional Study","volume":"184","author":"Mensah","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T Cell Exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","article-title":"CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer","volume":"37","author":"McLane","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.immuni.2018.04.026","article-title":"Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells","volume":"48","author":"Bengsch","year":"2018","journal-title":"Immunity"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/JLB.4MR0620-091R","article-title":"Unraveling Exhaustion in Adaptive and Conventional NK Cells","volume":"108","author":"Merino","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41423-019-0344-8","article-title":"Exhaustion and Senescence: Two Crucial Dysfunctional States of T Cells in the Tumor Microenvironment","volume":"17","author":"Zhao","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/imm.13464","article-title":"NK-Cell Exhaustion, B-Cell Exhaustion and T-Cell Exhaustion-the Differences and Similarities","volume":"166","author":"Roe","year":"2022","journal-title":"Immunology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/ni.1679","article-title":"Coregulation of CD8+ T Cell Exhaustion by Multiple Inhibitory Receptors during Chronic Viral Infection","volume":"10","author":"Blackburn","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e001849","DOI":"10.1136\/jitc-2020-001849","article-title":"Galectin-9 Expression Defines Exhausted T Cells and Impaired Cytotoxic NK Cells in Patients with Virus-Associated Solid Tumors","volume":"8","author":"Okoye","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_108","first-page":"e21549","article-title":"Role of TCF-1 in Differentiation, Exhaustion, and Memory of CD8+ T Cells: A Review","volume":"35","author":"Zhang","year":"2021","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1172\/JCI45816","article-title":"Human Breast Cancer Cells Enhance Self Tolerance by Promoting Evasion from NK Cell Antitumor Immunity","volume":"121","author":"Mamessier","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Bi, J., and Tian, Z. (2017). NK Cell Exhaustion. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00760"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Dao, T.N., Utturkar, S., Lanman, N.A., and Matosevic, S. (2020). TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation. Cancers, 12.","DOI":"10.3390\/cancers12092417"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jaci.2016.04.025","article-title":"Identification of a Subset of Human Natural Killer Cells Expressing High Levels of Programmed Death 1: A Phenotypic and Functional Characterization","volume":"139","author":"Pesce","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1172\/JCI125916","article-title":"Chronic Stimulation Drives Human NK Cell Dysfunction and Epigenetic Reprograming","volume":"129","author":"Merino","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1158\/2326-6066.CIR-13-0171","article-title":"Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade","volume":"2","author":"Gallois","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5758","DOI":"10.1182\/blood-2012-03-415364","article-title":"Rapid Development of Exhaustion and Down-Regulation of Eomesodermin Limit the Antitumor Activity of Adoptively Transferred Murine Natural Killer Cells","volume":"119","author":"Gill","year":"2012","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e183810","DOI":"10.1172\/jci.insight.183810","article-title":"Immune Exhaustion in ME\/CFS and Long COVID","volume":"9","author":"Rudd","year":"2024","journal-title":"JCI Insight"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"100720","DOI":"10.1016\/j.bbih.2023.100720","article-title":"Identification of CD8 T-Cell Dysfunction Associated with Symptoms in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) and Long COVID and Treatment with a Nebulized Antioxidant\/Anti-Pathogen Agent in a Retrospective Case Series","volume":"36","author":"Gil","year":"2023","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Karhan, E., Gunter, C.L., Ravanmehr, V., Horne, M., Kozhaya, L., Renzullo, S., Placek, L., George, J., Robinson, P.N., and Vernon, S.D. (2019). Perturbation of Effector and Regulatory T Cell Subsets in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). bioRxiv.","DOI":"10.1101\/2019.12.23.887505"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12967-022-03662-7","article-title":"Genetic and Epigenetic Regulation of Catechol-O-Methyltransferase in Relation to Inflammation in Chronic Fatigue Syndrome and Fibromyalgia","volume":"20","author":"Polli","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jad.2011.09.004","article-title":"Evidence for Inflammation and Activation of Cell-Mediated Immunity in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS): Increased Interleukin-1, Tumor Necrosis Factor-\u03b1, PMN-Elastase, Lysozyme and Neopterin","volume":"136","author":"Maes","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e2415119121","DOI":"10.1073\/pnas.2415119121","article-title":"Transcriptional Reprogramming Primes CD8+ T Cells toward Exhaustion in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"121","author":"Iu","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41467-024-45107-3","article-title":"Deep Phenotyping of Post-Infectious Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"15","author":"Walitt","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Steiner, S., Becker, S.C., Hartwig, J., Sotzny, F., Lorenz, S., Bauer, S., L\u00f6bel, M., Stittrich, A.B., Grabowski, P., and Scheibenbogen, C. (2020). Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME\/CFS With Infectious Onset. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00578"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/imr.12823","article-title":"T-Cell Exhaustion in HIV Infection","volume":"292","author":"Fenwick","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The Future of Immune Checkpoint Therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Faas, M.M., and de Vos, P. (2020). Mitochondrial Function in Immune Cells in Health and Disease. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165845"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s12079-019-00507-9","article-title":"Mitochondria: The Indispensable Players in Innate Immunity and Guardians of the Inflammatory Response","volume":"13","author":"Mohanty","year":"2019","journal-title":"J. Cell Commun. Signal"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Angajala, A., Lim, S., Phillips, J.B., Kim, J.-H., Yates, C., You, Z., and Tan, M. (2018). Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01605"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"164309","DOI":"10.1155\/2014\/164309","article-title":"Powering the Immune System: Mitochondria in Immune Function and Deficiency","volume":"2014","author":"Walker","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Gupta, S.S., Wang, J., and Chen, M. (2020). Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01013"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Schurich, A., and Henson, S.M. (2014). The Many Unknowns Concerning the Bioenergetics of Exhaustion and Senescence during Chronic Viral Infection. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00468"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e30938","DOI":"10.7554\/eLife.30938","article-title":"Long-Term Antigen Exposure Irreversibly Modifies Metabolic Requirements for T Cell Function","volume":"7","author":"Bettonville","year":"2018","journal-title":"Elife"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1128\/MCB.25.21.9543-9553.2005","article-title":"CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms","volume":"25","author":"Parry","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Saeidi, A., Zandi, K., Cheok, Y.Y., Saeidi, H., Wong, W.F., Lee, C.Y.Q., Cheong, H.C., Yong, Y.K., Larsson, M., and Shankar, E.M. (2018). T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02569"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12943-024-02175-9","article-title":"Targeting Mitochondria: Restoring the Antitumor Efficacy of Exhausted T Cells","volume":"23","author":"Yang","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1172\/JCI75051","article-title":"P38 Signaling Inhibits MTORC1-Independent Autophagy in Senescent Human CD8+ T Cells","volume":"124","author":"Henson","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e13067","DOI":"10.1111\/acel.13067","article-title":"Mitochondrial Mass Governs the Extent of Human T Cell Senescence","volume":"19","author":"Callender","year":"2020","journal-title":"Aging Cell"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ravenhill, S.M., Evans, A.H., and Crewther, S.G. (2023). Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson\u2019s Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12051117"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"168","DOI":"10.2174\/1570159X11666131120224653","article-title":"Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)\/Chronic Fatigue Syndrome (CFS)","volume":"12","author":"Morris","year":"2014","journal-title":"Curr. Neuropharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Missailidis, D., Sanislav, O., Allan, C.Y., Annesley, S.J., and Fisher, P.R. (2020). Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202002.0029.v1"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Maya, J., Leddy, S.M., Gottschalk, C.G., Peterson, D.L., and Hanson, M.R. (2023). Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032010"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1172\/JCI134985","article-title":"Can the Light of Immunometabolism Cut through \u201cBrain Fog\u201d?","volume":"130","author":"Hornig","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_143","first-page":"102","article-title":"Reduced Glycolytic Reserve in Isolated Natural Killer Cells from Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome Patients: A Preliminary Investigation","volume":"37","author":"Nguyen","year":"2019","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Armstrong, C.W., Mensah, F.F.K., Leandro, M.J., Reddy, V., Gooley, P.R., Berkovitz, S., and Cambridge, G. (2024). In Vitro B Cell Experiments Explore the Role of CD24, CD38, and Energy Metabolism in ME\/CFS. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1178882"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Mensah, F.F.K., Armstrong, C.W., Reddy, V., Bansal, A.S., Berkovitz, S., Leandro, M.J., and Cambridge, G. (2018). CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02421"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:45:18Z","timestamp":1760028318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":145,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["biom15030357"],"URL":"https:\/\/doi.org\/10.3390\/biom15030357","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,1]]}}}