{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:55:52Z","timestamp":1787748952083,"version":"build-2784847793"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271370"],"award-info":[{"award-number":["82271370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Ischemic stroke (IS) is a significant contributor to disability and death worldwide, with limited treatments beyond early intervention. The importance of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the advancement of IS has been highlighted by recent studies, providing new insights into immunomodulatory strategies. This review describes the spatiotemporal dynamics of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and their subsets at different stages of IS. The signaling pathways activated by IS regulate the distribution of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and their subsets, which further influences the inflammatory response and disease progression. In the acute and subacute stages, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells exacerbate neuronal damage. In contrast, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which are predominantly composed of Treg cells (Tregs), promote tissue repair and neurological recovery in the chronic stage. In light of recent findings that challenge traditional views, we analyze the underlying mechanisms and potential explanations for these discrepancies. In addition, we summarize the potential of targeting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells as a therapeutic strategy for IS. Although no drugs specifically targeting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells have been developed, certain drugs that modulate CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells show potential for IS treatment. Moreover, multitarget drugs integrated with nanomaterials are currently undergoing preclinical investigation. We further explore the challenges in the clinical translation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell-targeted therapies and discuss potential strategies to address these challenges. In conclusion, a deeper comprehension of the complex effects of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and their subsets on IS will contribute to disease management and drug development, thereby improving the quality of life for IS patients.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1512634","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T01:25:31Z","timestamp":1745544331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["CD4+ T cells in ischemic stroke: effects and therapeutic targets"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhengqi","family":"Lian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yikun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1212\/WNL.0000000000012781","article-title":"Global epidemiology of stroke and access to acute ischemic stroke interventions","volume":"97","author":"Saini","year":"2021","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.3362","article-title":"Trends in reperfusion therapy for in-hospital ischemic stroke in the endovascular therapy era","volume":"77","author":"Akbik","year":"2020","journal-title":"JAMA neurology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30078-X","article-title":"Global brain inflammation in stroke","volume":"18","author":"Shi","year":"2019","journal-title":"Lancet Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s42466-020-00060-6","article-title":"Recovery from stroke: current concepts and future perspectives","volume":"2","author":"Grefkes","year":"2020","journal-title":"Neurological Res practice"},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/jcbfm.1995.5","article-title":"Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex","volume":"15","author":"Jander","year":"1995","journal-title":"J Cereb Blood Flow Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.707972","article-title":"T cell response in ischemic stroke: from mechanisms to translational insights","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1756286418774254","DOI":"10.1177\/1756286418774254","article-title":"Danger signals in stroke and their role on microglia activation after ischemia","volume":"11","author":"G\u00fclke","year":"2018","journal-title":"Ther Adv neurological Disord"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319994","article-title":"Immune pathways in etiology, acute phase, and chronic sequelae of ischemic stroke","volume":"130","author":"Endres","year":"2022","journal-title":"Circ Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0824-5","article-title":"Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery","volume":"565","author":"Ito","year":"2019","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.v88:11","article-title":"Immunodeficiency reduces neural stem\/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke","volume":"88","author":"Saino","year":"2010","journal-title":"J Neurosci Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1756286418789854","DOI":"10.1177\/1756286418789854","article-title":"Anti-inflammatory treatments for stroke: from bench to bedside","volume":"11","author":"Drieu","year":"2018","journal-title":"Ther Adv neurological Disord"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/23969873221098857","article-title":"Preventing post-stroke dementia. 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