{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:59:07Z","timestamp":1787889547764,"version":"build-2784847793"},"reference-count":67,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["19K18323"],"award-info":[{"award-number":["19K18323"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["18K16544"],"award-info":[{"award-number":["18K16544"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["19K09147"],"award-info":[{"award-number":["19K09147"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["19K09414"],"award-info":[{"award-number":["19K09414"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Overactivated microglia play a key role in sepsis-associated encephalopathy (SAE), although the involvement of T cells is unclear. \u03b3\u03b4T cells in the brain and meninges regulate normal fear responses via interleukin (IL)-17 in healthy mice. In our sepsis model, the mice showed exacerbated anxious behavior at 10 days post-induction (dpi). At 8 dpi, IL-17 mRNA was significantly upregulated in the brains of septic mice compared with those of control mice. Simultaneously, the number of \u03b3\u03b4T cells increased in the brains of septic mice in a severity-dependent manner. Additionally, IL-17-producing \u03b3\u03b4T cells, expressing both the C-X-C motif receptor (CXCR) 6 and the C-C motif receptor (CCR) 6, increased in mice brains, dependent on the severity of sepsis. The frequency of \u03b3\u03b4T cells in the meninges fluctuated similarly to that in the brain, peaking at 8 dpi of sepsis. Behavioral tests were performed on septic mice after the continuous administration of anti-\u03b3\u03b4TCR (\u03b1-\u03b3\u03b4TCR) or anti-IL-17A (\u03b1-IL-17A) antibodies to deplete the \u03b3\u03b4T cells and IL-17A, respectively. Compared with IgG-treated septic mice, \u03b1-\u03b3\u03b4TCR- and \u03b1-IL-17A-treated septic mice showed suppressed microglial activation and improvements in anxious behavior. These results suggested that CCR6+CXCR6+ IL-17-producing \u03b3\u03b4T cells in the brain and meninges promote the exacerbation of SAE and sepsis-induced psychological disorders in mice.<\/jats:p>","DOI":"10.3390\/jcm12134309","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:45:11Z","timestamp":1687913111000},"page":"4309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Increased Interleukin-17-Producing \u03b3\u03b4T Cells in the Brain Exacerbate the Pathogenesis of Sepsis-Associated Encephalopathy and Sepsis-Induced Anxiety in Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Naoki","family":"Moriyama","sequence":"first","affiliation":[{"name":"Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-3042","authenticated-orcid":false,"given":"Yuko","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-7138","authenticated-orcid":false,"given":"Kimihiro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Aoi","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"},{"name":"Division of Advanced Medical Science, Kobe University Graduate School of Science, Technology and Innovation, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"},{"name":"Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Kotani","sequence":"additional","affiliation":[{"name":"Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1097\/CCM.0000000000005357","article-title":"Executive summary: Surviving sepsis campaign: International guidelines for the management of sepsis and septic shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit. 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