{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T09:27:51Z","timestamp":1793611671726,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute ischemic stroke is accompanied by marked peripheral and central immune imbalance, in which disruption of the Th17\/Treg axis is considered an important driver of aggravated neuroinflammation and secondary injury, yet the upstream regulatory pathways amenable to intervention remain unclear. We hypothesised that the probiotic\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    (AKK) could be linked to post\u2010stroke immune remodelling and neuroprotection by influencing intestinal epithelial signalling. Using a tMCAO mouse model combined with AKK intervention, SIRT1 inhibition, IL\u201017\u2010deficient conditions, and IL\u201017 neutralisation\/rescue experiments, we systematically assessed intestinal barrier integrity, peripheral and central immune responses, and neurological injury, together with single\u2010cell transcriptomic and ATAC\u2010seq analyses of the Th17\/Treg axis. Complementary human and murine intestinal epithelial\u2013T cell co\u2010culture systems and a neuronal OGD model were used for functional mechanistic assessment. AKK was associated with activation of AMPK\/SIRT1 signalling, decreased Th17 proportions, increased Treg levels, suppression of IL\u201017\u2010associated inflammatory responses, and enhancement of IL\u201010 signalling, thereby improving systemic and intracerebral inflammatory environments. In the neuronal OGD model, IL\u201017 neutralisation alone provided partial protection, combined AKK and IL\u201017 blockade further enhanced neuroprotection, and recombinant IL\u201017 rescue attenuated, but did not fully define, the protective effects of AKK. AKK also protected intestinal barrier integrity, reduced infarct volume, and improved neurological function. Together, these findings support a contributory gut epithelial AMPK\/SIRT1\u2010associated immunoregulatory network in which AKK is linked to Th17\/Treg immune remodelling and reduced post\u2010stroke neuroinflammation through the gut\u2010immune\u2010brain axis, while IL\u201017 signalling appears to represent one important component rather than an exclusive pathway.\n                  <\/jats:p>","DOI":"10.1111\/imm.70191","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:17:56Z","timestamp":1788347876000},"page":"647-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Epithelial\n                    <scp>AMPK<\/scp>\n                    \/\n                    <scp>SIRT1<\/scp>\n                    Signalling Is Associated With\n                    <scp>\n                      <i>Akkermansia muciniphila<\/i>\n                    <\/scp>\n                    \u2010Linked Th17\/Treg Reprogramming and Immune Homeostasis After Ischemic Stroke"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6426-2669","authenticated-orcid":false,"given":"Jianfeng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Putian University  Putian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Putian University  Putian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duxiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Putian University  Putian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Putian University  Putian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengxing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Putian University  Putian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012781"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207387"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010020\u201000844\u20103"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2024.1400808"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010021\u201002177\u20100"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e32171"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1080737"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135530"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010023\u201003723\u2010y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13611"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010018\u20103250\u20104"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13265"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051353\u20102"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR\u2010D\u201024\u201001363"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1008514"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.845243"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.678355"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2025.102111"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.25259\/SNI_703_2024"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103676"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42466\u2010022\u201000222\u20108"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1141387"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00503\u201024"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010024\u201010146\u20106"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14040764"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00796\u201010"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010024\u201002001\u2010w"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219451110"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272\u2010025\u201001576\u20108"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201062631\u2010y"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020915"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010022\u201001096\u20103"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15070920"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071239"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2022.2044286"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR\u2010D\u201025\u201000701"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010025\u201004224\u20106"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70657"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010022\u201000691\u20102"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:49:00Z","timestamp":1793609340000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["10.1111\/imm.70191"],"URL":"https:\/\/doi.org\/10.1111\/imm.70191","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"e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