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Despite advances in reperfusion therapy, effective treatments targeting secondary neuroinflammation remain limited. Accumulating evidence indicates that \u03b3\u03b4 T cells, particularly through the production of interleukin (IL)\u201017, contribute to ischemic brain injury. As the intestine represents a major reservoir of \u03b3\u03b4 T cells, brain\u2013gut communication may connect intestinal immune alterations with post\u2010stroke neuroinflammation. This review examines the role of \u03b3\u03b4 T cells in ischemic stroke from the perspective of the brain\u2013gut axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We synthesized current mechanistic evidence from experimental, translational, and clinical studies concerning \u03b3\u03b4 T\u2010cell activation and recruitment after ischemic stroke. Particular attention was given to IL\u201017\u2010mediated neuroinflammation, intestinal barrier dysfunction, gut microbiota dysbiosis, and bidirectional immune communication between the ischemic brain and the intestine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following ischemic stroke, \u03b3\u03b4 T cells are activated and recruited to the injured brain, where their production of IL\u201017 promotes neuroinflammation, blood\u2013brain barrier disruption, and secondary tissue injury. Concurrently, cerebral ischemia induces autonomic, immune, and metabolic disturbances that alter the gut microbiota and compromise intestinal barrier integrity. These changes may facilitate microbial product translocation and systemic inflammation, thereby amplifying cerebral inflammatory responses. Gut\u2010resident \u03b3\u03b4 T cells may participate in this process by regulating mucosal immunity and IL\u201017\u2010associated inflammatory signaling. Together, these mechanisms may establish a self\u2010reinforcing brain\u2013gut injury cycle. However, direct evidence defining the contributions, trafficking patterns, and functional heterogeneity of specific intestinal \u03b3\u03b4 T\u2010cell subsets in ischemic brain injury remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\u03b3\u03b4 T cells may serve as important immunological mediators linking intestinal dysfunction to neuroinflammation after ischemic stroke. Therapeutic strategies targeting \u03b3\u03b4 T\u2010cell activation, IL\u201017 signaling, intestinal barrier disruption, or gut microbiota dysbiosis may help interrupt the brain\u2013gut injury cycle. Future studies integrating lineage tracing, single\u2010cell and spatial profiling, and tissue\u2010specific interventions are required to distinguish the roles of brain\u2010infiltrating and gut\u2010resident \u03b3\u03b4 T\u2010cell subsets and facilitate the clinical translation of brain\u2013gut axis\u2010based therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71092","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:32:13Z","timestamp":1787052733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of \u03b3\u03b4 T Cells in Ischemic Stroke: Insights From the Perspective of the Brain\u2013Gut Axis"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0098-3295","authenticated-orcid":false,"given":"Yilin","family":"Li","sequence":"first","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Li","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5251-1977","authenticated-orcid":false,"given":"Yang","family":"Shen","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yikun","family":"Gao","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-5789","authenticated-orcid":false,"given":"Zhihong","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-8772","authenticated-orcid":false,"given":"Lijuan","family":"Gu","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-412726"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1999"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1206299"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4068"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2019.04.097"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9726"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2781"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00654"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1273459"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315592121"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1148988"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02636"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.101"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891687"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.849954"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.623451"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.013"},{"key":"e_1_2_12_19_1","article-title":"Th17 Cells, Gammadelta T Cells and Their Interplay in EAE and Multiple Sclerosis","author":"McGinley A. 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