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The interplay between peripheral CD4<jats:sup>+<\/jats:sup> T cells and central microglia orchestrates the \u201csystemic\u2010central\u201d immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed\u00a0an imbalance in Th1\/Th2 subsets in the periphery\uff0caccompanied by\u00a0related cytokines release in TLE patients. they proposed that this peripheral Th1\/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li\u2010pilocarpine\u2010induced TLE rats, a peripheral Th1\/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4<jats:sup>+<\/jats:sup> T cells infiltrated through the compromised blood\u2010brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4<jats:sup>+<\/jats:sup> T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1\/Th2 differentiation, CD4<jats:sup>+<\/jats:sup> T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1\/Th2 imbalance in modulating the \u201csystemic\u2010central\u201d response in TLE, highlighting Notch1 as a potential therapeutic target.<\/jats:p>","DOI":"10.1002\/advs.202405346","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T04:06:03Z","timestamp":1723521963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Th1\/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression"],"prefix":"10.1002","volume":"11","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"Department of Neurology Guizhou Provincial People's Hospital  Guiyang Guizhou 550002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Operative Dentistry and Endodontics West China Hospital of Stomatology Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Immuno\u2010Oncology City of Hope  Los Angeles CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology First Affiliated Hospital Kunming Medical University  Kunming Yunnan 650032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7658-1399","authenticated-orcid":false,"given":"Li","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.020"},{"key":"e_1_2_9_2_1","first-page":"412","volume":"402","author":"Asadi\u2010Pooya A. 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