{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:15:21Z","timestamp":1777421721312,"version":"3.51.4"},"reference-count":120,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PAPIIT-DGAPA","award":["IN-204324"],"award-info":[{"award-number":["IN-204324"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Chronic exposure to low concentrations of ozone leads to oxidative stress, which disrupts immune regulation. The thymus gland plays a crucial role in the maturation and differentiation of T lymphocytes, cells essential for the body\u2019s defense and immune tolerance. In the early years of life, the thymus is highly active, but after adolescence, it undergoes a process known as thymic involution. This process involves a reduction in the size and functionality of the thymus, which is gradually replaced by adipose tissue. Ozone pollution exacerbates this involution and impairs the thymus\u2019s proper function. Consequently, thymic cells may alter their function, leading to a decreased production and diversity of T lymphocytes. This decrease contributes to the establishment of chronic inflammatory states, autoimmunity, and a reduced capacity to respond to infections. Immune dysfunction and chronic inflammation can further result in the development and progression of neurodegenerative diseases. Moreover, thymic involution, exacerbated by environmental factors and oxidative stress, negatively impacts overall immunity and accelerates the progression of degenerative diseases over time. This review aims to explore the relationship between oxidative stress and its impact on the thymus gland. We hypothesize that understanding the relationship between ozone pollution and disruption of the redox\u2013immune axis is crucial for understanding the role of the thymus in senescence and neurodegenerative diseases. To explore this topic, we conducted a review from 2006 to 2025, utilizing several databases, including PubMed, Scopus, Google Scholar, EBSCO, and Web of Science.<\/jats:p>","DOI":"10.3390\/medsci13040293","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:31:46Z","timestamp":1764689506000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Redox-Immune Axis and Ozone Pollution: From Oxidative Stress to Thymic Involution and Neurodegeneration"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-2427","authenticated-orcid":false,"given":"Marlen","family":"Vald\u00e9s-Fuentes","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5204-1416","authenticated-orcid":false,"given":"Selva","family":"Rivas-Arancibia","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105998","DOI":"10.1016\/j.envint.2020.105998","article-title":"Long-term exposure to NO(2) and O(3) and all-cause and respiratory mortality: A systematic review and meta-analysis","volume":"144","author":"Huangfu","year":"2020","journal-title":"Environ. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/S1352-2310(99)00478-1","article-title":"Ozone and other secondary photochemical pollutants: Chemical processes governing their formation in the planetary boundary layer","volume":"34","author":"Jenkin","year":"2000","journal-title":"Atmos. Environ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/toxsci\/kfp252","article-title":"Oxidative stress caused by ozone exposure induces loss of brain repair in the hippocampus of adult rats","volume":"113","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_4","first-page":"503","article-title":"Systemic Th17\/IL-17A response appears prior to hippocampal neurodegeneration in rats exposed to low doses of ozone","volume":"34","year":"2019","journal-title":"Neurologia"},{"key":"ref_5","unstructured":"World Health Organization (2021). WHO Global Air Quality Guidelines: Particulate Matter (PM2. 5 and PM10), Ozone, Nitrogen Dioxide, Sulfur Dioxide and Carbon Monoxide: Executive Summary, WHO."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2035117","DOI":"10.1080\/21645515.2022.2035117","article-title":"Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders\u2014Advances and challenges","volume":"18","author":"Goswami","year":"2022","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_7","first-page":"277","article-title":"Ozone pollution, oxidative stress, synaptic plasticity, and neurodegeneration","volume":"37","year":"2022","journal-title":"Neurologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7986071","DOI":"10.1155\/2020\/7986071","article-title":"Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution","volume":"2020","author":"Barbouti","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1002\/eji.202249915","article-title":"Trappc1 deficiency impairs thymic epithelial cell development by breaking endoplasmic reticulum homeostasis","volume":"52","author":"Dong","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"ref_10","first-page":"320","article-title":"Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)\/protein kinase B (Akt) pathway","volume":"18","author":"Pavlovic","year":"2018","journal-title":"Bosn. J. Basic. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41590-020-00834-9","article-title":"Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion","volume":"22","author":"Scharping","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1038\/s41467-019-11879-2","article-title":"Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration","volume":"10","author":"Venables","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110363","DOI":"10.1016\/j.celrep.2022.110363","article-title":"Redox regulation of age-associated defects in generation and maintenance of T cell self-tolerance and immunity to foreign antigens","volume":"38","author":"Hester","year":"2022","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10522-019-09816-3","article-title":"Sexual dimorphism in rat thymic involution: A correlation with thymic oxidative status and inflammation","volume":"20","author":"Sopta","year":"2019","journal-title":"Biogerontology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7784","DOI":"10.1038\/s41467-024-51767-y","article-title":"Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S1074-7613(02)00267-4","article-title":"Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus","volume":"16","author":"Ueno","year":"2002","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13671","DOI":"10.1111\/acel.13671","article-title":"Age-related thymic involution: Mechanisms and functional impact","volume":"21","author":"Liang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shichkin, V.P., and Antica, M. (2022). Key Factors for Thymic Function and Development. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.926516"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.18632\/aging.100122","article-title":"The role of the thymus in immunosenescence: Lessons from the study of thymectomized individuals","volume":"2","author":"Appay","year":"2010","journal-title":"Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1056\/NEJMoa2302892","article-title":"Health Consequences of Thymus Removal in Adults. Reply","volume":"389","author":"Kooshesh","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"P\u00e9rez, M.R., Vandenabeele, P., and Tougaard, P. (2024). The thymus road to a T cell: Migration, selection, and atrophy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1443910"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.it.2017.07.010","article-title":"The Mechanisms of T Cell Selection in the Thymus","volume":"38","author":"Takaba","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and aging: Signaling pathways and intervention therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e140313","DOI":"10.1172\/jci.insight.140313","article-title":"Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation","volume":"5","author":"Oh","year":"2020","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Shevyrev, D., and Tereshchenko, V. (2019). Treg Heterogeneity, Function, and Homeostasis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.03100"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41392-025-02371-z","article-title":"Immunosenescence: Signaling pathways, diseases and therapeutic targets","volume":"10","author":"Fu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12979-020-0173-8","article-title":"Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging","volume":"17","author":"Thomas","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7116","DOI":"10.18632\/oncotarget.12572","article-title":"Friend or foe: The dichotomous impact of T cells on neuro-de\/re-generation during aging","volume":"8","author":"Coder","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kologrivova, I.V., Naryzhnaya, N.V., and Suslova, T.E. (2024). Thymus in Cardiometabolic Impairments and Atherosclerosis: Not a Silent Player?. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071408"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.nut.2015.05.014","article-title":"Oxidative damage and antioxidant defense in thymus of malnourished lactating rats","volume":"31","year":"2015","journal-title":"Nutrition"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12853","DOI":"10.1111\/sji.12853","article-title":"Regulatory T cells and co-evolution of allele-specific MHC recognition by the TCR","volume":"91","author":"Steele","year":"2020","journal-title":"Scand. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1146\/annurev-immunol-090222-101050","article-title":"Aire in Autoimmunity","volume":"42","author":"Miller","year":"2024","journal-title":"Annu. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2204296119","DOI":"10.1073\/pnas.2204296119","article-title":"Redox status regulates autophagy in thymic stromal cells and promotes T cell tolerance","volume":"119","author":"Semwal","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.celrep.2015.07.008","article-title":"Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency","volume":"12","author":"Griffith","year":"2015","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1089\/15230860260196155","article-title":"Redox control of T-cell death","volume":"4","author":"Nakashima","year":"2002","journal-title":"Antioxid. Redox Signal"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17686","DOI":"10.1073\/pnas.1012016107","article-title":"Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species","volume":"107","author":"Kraaij","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41423-022-00902-0","article-title":"Redox regulation of the immune response","volume":"19","author":"Morris","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jemt.10410","article-title":"Thymic epithelial cells in age-dependent involution","volume":"62","year":"2003","journal-title":"Microsc. Res. Tech."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1365-2567.2007.02555.x","article-title":"Immunosenescence: Emerging challenges for an ageing population","volume":"120","author":"Aw","year":"2007","journal-title":"Immunology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112900","DOI":"10.1016\/j.intimp.2024.112900","article-title":"Immunosenescence: A new direction in anti-aging research","volume":"141","author":"Li","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1084\/jem.20140857","article-title":"T cell lipid peroxidation induces ferroptosis and prevents immunity to infection","volume":"212","author":"Matsushita","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1002\/eji.200424962","article-title":"Reactive oxygen species induced by the deletion of peroxiredoxin II (PrxII) increases the number of thymocytes resulting in the enlargement of PrxII-null thymus","volume":"34","author":"Moon","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e2249948","DOI":"10.1002\/eji.202249948","article-title":"The thioredoxin system: Balancing redox responses in immune cells and tumors","volume":"53","author":"Muri","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1093\/carcin\/bgl111","article-title":"Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles","volume":"27","author":"Cassidy","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1752-153X-7-150","article-title":"Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion","volume":"7","author":"Dias","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Carr, A.C., and Maggini, S. (2017). Vitamin C and Immune Function. Nutrients, 9.","DOI":"10.3390\/nu9111211"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/biof.5520070111","article-title":"The role of vitamin E in T-cell differentiation and the decrease of cellular immunity with aging","volume":"7","author":"Moriguchi","year":"1998","journal-title":"Biofactors"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bono, M.R., Tejon, G., Flores-Santiba\u00f1ez, F., Fernandez, D., Rosemblatt, M., and Sauma, D. (2016). Retinoic Acid as a Modulator of T Cell Immunity. Nutrients, 8.","DOI":"10.3390\/nu8060349"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.1158\/0008-5472.CAN-04-1586","article-title":"Uric acid promotes tumor immune rejection","volume":"64","author":"Hu","year":"2004","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S459","DOI":"10.33549\/physiolres.933202","article-title":"Hyperbilirubinemia decreases physiological markers in adjuvant-induced arthritis","volume":"64","author":"Bauerova","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.jnutbio.2013.02.003","article-title":"Resveratrol inhibits the deleterious effects of diet-induced obesity on thymic function","volume":"24","author":"Gulvady","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00210-020-01945-8","article-title":"Curcumin protects thymus against D-galactose-induced senescence in mice","volume":"394","author":"Li","year":"2021","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/eji.201142305","article-title":"Molecular control over thymic involution: From cytokines and microRNA to aging and adipose tissue","volume":"42","author":"Dooley","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sidler, C., W\u00f3ycicki, R., Ilnytskyy, Y., Metz, G., Kovalchuk, I., and Kovalchuk, O. (2013). Immunosenescence is associated with altered gene expression and epigenetic regulation in primary and secondary immune organs. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00211"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mad.2018.02.005","article-title":"In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution","volume":"177","author":"Barbouti","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/j.peptides.2010.07.026","article-title":"Thymosin alpha 1: Biological activities, applications and genetic engineering production","volume":"31","author":"Li","year":"2010","journal-title":"Peptides"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Savino, W., and Lepletier, A. (2023). Thymus-derived hormonal and cellular control of cancer. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1168186"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-immunol-042617-053019","article-title":"Unraveling the Complex Interplay Between T Cell Metabolism and Function","volume":"36","author":"Geltink","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/00039896.1991.9937430","article-title":"Ambient level ozone effects on subpopulations of thymocytes and spleen T lymphocytes","volume":"46","author":"Li","year":"1991","journal-title":"Arch. Environ. Health"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/S0013-9351(86)80154-2","article-title":"Thymus and pulmonary lymph node response to acute and subchronic ozone inhalation in the mouse","volume":"41","author":"Dziedzic","year":"1986","journal-title":"Environ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/cdd.2016.123","article-title":"Transient mitochondrial DNA double strand breaks in mice cause accelerated aging phenotypes in a ROS-dependent but p53\/p21-independent manner","volume":"24","author":"Pinto","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"320513","DOI":"10.1155\/2014\/320513","article-title":"Saponins from Aralia taibaiensis attenuate D-galactose-induced aging in rats by activating FOXO3a and Nrf2 pathways","volume":"2014","author":"Li","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"389","DOI":"10.18632\/aging.100043","article-title":"Mitochondria-targeted antioxidant SkQ1 inhibits age-dependent involution of the thymus in normal and senescence-prone rats","volume":"1","author":"Obukhova","year":"2009","journal-title":"Aging"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1017\/S0007114514003857","article-title":"High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice","volume":"113","author":"Uchio","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1126\/science.1106653","article-title":"Extension of murine life span by overexpression of catalase targeted to mitochondria","volume":"308","author":"Schriner","year":"2005","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-1-62703-239-1_3","article-title":"Senescence regulation by the p53 protein family","volume":"965","author":"Qian","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Passos, J.F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C.J., Miwa, S., Olijslagers, S., Hallinan, J., and Wipat, A. (2010). Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol. Syst. Biol., 6.","DOI":"10.1038\/msb.2010.5"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1365-2443.2003.00620.x","article-title":"Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway","volume":"8","author":"Iwasa","year":"2003","journal-title":"Genes. Cells"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tins.2009.03.003","article-title":"Immune senescence and brain aging: Can rejuvenation of immunity reverse memory loss?","volume":"32","author":"Schwartz","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102540","DOI":"10.1016\/j.arr.2024.102540","article-title":"Immunosenescence and inflammaging: Mechanisms and role in diseases","volume":"101","author":"Ajoolabady","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s12974-021-02308-7","article-title":"CD4+ effector T cells accelerate Alzheimer\u2019s disease in mice","volume":"18","author":"Machhi","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5825","DOI":"10.4049\/jimmunol.1500082","article-title":"Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation","volume":"194","author":"Coder","year":"2015","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Hayama, M., Ishii, H., Miyauchi, M., Yoshida, M., Hagiwara, N., Muramtatu, W., Namiki, K., Endo, R., Miyao, T., and Akiyama, N. (2024). Direct and indirect RANK and CD40 signaling regulate the maintenance of thymic epithelial cell frequency and properties in the adult thymus. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1500908"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41423-023-01064-3","article-title":"Regulation of CD8(+) T memory and exhaustion by the mTOR signals","volume":"20","author":"Chen","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2018.02.003","article-title":"NLRP3 inflammasome activation in the thymus of MPTP-induced Parkinsonian mouse model","volume":"288","author":"Wen","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1128\/MCB.21.19.6615-6625.2001","article-title":"Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells","volume":"21","author":"Narimatsu","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.mcna.2016.09.005","article-title":"Anemia of Inflammation: A Review","volume":"101","author":"Fraenkel","year":"2017","journal-title":"Med. Clin. North. Am."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hong, Z., Mei, J., Guo, H., Zhu, J., and Wang, C. (2022). Intervention of cGAS\u2013STING signaling in sterile inflammatory diseases. J. Mol. Cell Biol., 14.","DOI":"10.1093\/jmcb\/mjac005"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e20230894","DOI":"10.1084\/jem.20230894","article-title":"Generation and repair of thymic epithelial cells","volume":"221","author":"Anderson","year":"2024","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Dhamne, C., Chung, Y., Alousi, A.M., Cooper, L.J., and Tran, D.Q. (2013). Peripheral and thymic foxp3(+) regulatory T cells in search of origin, distinction, and function. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00253"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Alvarez, F., Liu, Z., Bay, A., and Piccirillo, C.A. (2024). Deciphering the developmental trajectory of tissue-resident Foxp3(+) regulatory T cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1331846"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.it.2015.04.006","article-title":"Regulatory T cell identity: Formation and maintenance","volume":"36","author":"Li","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.4049\/jimmunol.181.4.2277","article-title":"Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression","volume":"181","author":"Xiao","year":"2008","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.2012.06492.x","article-title":"Glycobiology of immune responses","volume":"1253","author":"Rabinovich","year":"2012","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/icb.2010.142","article-title":"Finding their niche: Chemokines directing cell migration in the thymus","volume":"89","author":"Bunting","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.coi.2011.05.007","article-title":"Inflammation and mesenchymal stem cell aging","volume":"23","author":"Lepperdinger","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chen, Y., Colello, J., Jarjour, W., and Zheng, S.G. (2019). Cellular Metabolic Regulation in the Differentiation and Function of Regulatory T Cells. Cells, 8.","DOI":"10.3390\/cells8020188"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jneuroim.2010.02.005","article-title":"Thymic involution and proliferative T-cell responses in multiple sclerosis","volume":"221","author":"Duszczyszyn","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.4049\/jimmunol.1403243","article-title":"Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-\u03b2 Therapy","volume":"194","author":"Rasouli","year":"2015","journal-title":"J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.cell.2020.09.054","article-title":"HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis","volume":"183","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vlaming, M., Bilemjian, V., Freile, J., Lourens, H.J., van Rooij, N., Huls, G., van Meerten, T., de Bruyn, M., and Bremer, E. (2021). CD20 positive CD8 T cells are a unique and transcriptionally-distinct subset of T cells with distinct transmigration properties. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00007-0"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1038\/s41467-021-22230-z","article-title":"The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5","volume":"12","author":"Radomir","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s13760-012-0061-x","article-title":"Self-tolerance in multiple sclerosis","volume":"112","author":"Gonsette","year":"2012","journal-title":"Acta Neurol. Belg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e13511","DOI":"10.1111\/acel.13511","article-title":"Insights into T-cell dysfunction in Alzheimer\u2019s disease","volume":"20","author":"Dai","year":"2021","journal-title":"Aging Cell"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Rivas-Arancibia, S., Rodr\u00edguez-Mart\u00ednez, E., Vald\u00e9s-Fuentes, M., Miranda-Mart\u00ednez, A., Hern\u00e1ndez-Orozco, E., and Res\u00e9ndiz-Ramos, C. (2024). Changes in SOD and NF-\u03baB Levels in Substantia Nigra and the Intestine through Oxidative Stress Effects in a Wistar Rat Model of Ozone Pollution. Antioxidants, 13.","DOI":"10.20944\/preprints202403.1299.v1"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s12017-023-08739-0","article-title":"IL-17A Facilitates Entry of Autoreactive T-Cells and Granulocytes into the CNS During EAE","volume":"25","author":"Zimmermann","year":"2023","journal-title":"Neuromolecular Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/B978-0-444-52001-2.00003-0","article-title":"The good and the bad of neuroinflammation in multiple sclerosis","volume":"122","author":"Naegele","year":"2014","journal-title":"Handb. Clin. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.bbi.2016.02.009","article-title":"T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer\u2019s disease-like cerebral amyloidosis","volume":"54","author":"Ferretti","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1615\/CritRevImmunol.2023050145","article-title":"The Role of T Cells in Alzheimer\u2019s Disease Pathogenesis","volume":"43","author":"Zhao","year":"2023","journal-title":"Crit. Rev. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","article-title":"Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/s41467-020-15626-w","article-title":"\u03b1-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson\u2019s disease","volume":"11","author":"Dhanwani","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"S137","DOI":"10.3233\/JPD-223153","article-title":"Neuronal Presentation of Antigen and Its Possible Role in Parkinson\u2019s Disease","volume":"12","author":"Hobson","year":"2022","journal-title":"J. Parkinsons Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12974-021-02287-9","article-title":"T lymphocyte senescence is attenuated in Parkinson\u2019s disease","volume":"18","author":"Kouli","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bbi.2010.12.004","article-title":"Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer\u2019s disease","volume":"25","author":"Saresella","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Oberstein, T.J., Taha, L., Spitzer, P., Hellstern, J., Herrmann, M., Kornhuber, J., and Maler, J.M. (2018). Imbalance of Circulating T(h)17 and Regulatory T Cells in Alzheimer\u2019s Disease: A Case Control Study. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01213"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s11845-018-1793-2","article-title":"Evaluation of regulatory T lymphocytes and IL2Ra and FOXP3 gene expression in peripheral mononuclear cells from patients with amyotrophic lateral sclerosis","volume":"187","author":"Tafakhori","year":"2018","journal-title":"Ir. J. Med. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2022.06.004","article-title":"Blocking immune cell infiltration of the central nervous system to tame Neuroinflammation in Amyotrophic lateral sclerosis","volume":"105","author":"Garofalo","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1523\/JNEUROSCI.2745-14.2015","article-title":"Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines IL-1\u03b2 and TNF-\u03b1","volume":"35","author":"Hennessy","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Marcovecchio, G.E., Ferrua, F., Fontana, E., Beretta, S., Genua, M., Bortolomai, I., Conti, A., Montin, D., Cascarano, M.T., and Bergante, S. (2021). Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.669893"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1248\/cpb.c24-00069","article-title":"Anti-amyloid-\u03b2 Antibodies and Anti-tau Therapies for Alzheimer\u2019s Disease: Recent Advances and Perspectives","volume":"72","author":"Suzuki","year":"2024","journal-title":"Chem Pharm Bull (Tokyo)"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13024-023-00692-7","article-title":"Amyloid-\u03b2 specific regulatory T cells attenuate Alzheimer\u2019s disease pathobiology in APP\/PS1 mice","volume":"18","author":"Yeapuri","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.molimm.2016.12.005","article-title":"Acute arsenic exposure induces inflammatory responses and CD4(+) T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2","volume":"81","author":"Duan","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s12011-016-0860-7","article-title":"Selenium Deficiency Induces Autophagy in Immune Organs of Chickens","volume":"177","author":"Khoso","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/cdd.2008.59","article-title":"BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development","volume":"15","author":"Arsov","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10571-015-0166-x","article-title":"ROS and Autophagy: Interactions and Molecular Regulatory Mechanisms","volume":"35","author":"Li","year":"2015","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.coi.2009.08.007","article-title":"AIRE in the thymus and beyond","volume":"21","author":"Gardner","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eadm9582","DOI":"10.1126\/sciadv.adm9582","article-title":"Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling","volume":"10","author":"Artusa","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/eji.200738052","article-title":"Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input","volume":"38","author":"White","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s00774-020-01178-y","article-title":"Regulation of T cell-associated tissues and T cell activation by RANKL-RANK-OPG","volume":"39","author":"Walsh","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"878030","DOI":"10.1155\/2012\/878030","article-title":"Nrf2\/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS","volume":"2012","author":"Petri","year":"2012","journal-title":"Neurol. Res. Int."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/4\/293\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:53:50Z","timestamp":1764690830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/4\/293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,29]]},"references-count":120,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["medsci13040293"],"URL":"https:\/\/doi.org\/10.3390\/medsci13040293","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,29]]}}}