{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:48Z","timestamp":1791557628950,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302508"],"award-info":[{"award-number":["82302508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170636"],"award-info":[{"award-number":["82170636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2305100"],"award-info":[{"award-number":["2022YFC2305100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2304401"],"award-info":[{"award-number":["2022YFC2304401"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2026ZD01912201"],"award-info":[{"award-number":["2026ZD01912201"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Liver sinusoidal endothelial cells (LSECs) are liver\u2010resident antigen\u2010presenting cells that induce immune tolerance, a feature exploited by persistent viruses. Toll\u2010like receptor (TLR) ligands can override this tolerance, but whether metabolic reprogramming underlies LSEC activation remains unknown. We investigated whether TLR ligand\u2010induced functional changes in LSECs require glycolysis and explored the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LSECs from wild\u2010type and chronic hepatitis B virus (HBV) replication mice were stimulated with TLR2 ligand P3C or TLR9 ligand ODN1826. LSEC maturation, cytokine production and T cell\u2010priming capacity were assessed. Glycolytic flux was measured by metabolomics and Seahorse analysis. The glycolysis inhibitor 2\u2010deoxy\u2010D\u2010glucose (2\u2010DG) was used, and mTORC1 pathway involvement was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The TLR2 ligand P3C promoted LSEC maturation, while the TLR9 ligand ODN1826 enhanced IL\u201012 production. Both ligands potentiated LSEC\u2010induced T cell responses. In LSECs isolated from a mouse model of chronic HBV replication, P3C and ODN1826 also induced maturation and enhanced T cell\u2010activating capacity, albeit to a weaker extent. Metabolomics and Seahorse analyses revealed that TLR2\/9 ligands enhanced glycolysis and oxidative phosphorylation in LSECs, accompanied by activation of the mTORC1\/HIF\u20101\u03b1\/c\u2010Myc axis. Blocking glycolysis with 2\u2010DG significantly reduced co\u2010stimulatory molecule expression on P3C\u2010stimulated LSECs and IL\u201012 production by ODN1826\u2010stimulated LSECs in both wild\u2010type and chronic HBV models. Mechanistically, 2\u2010DG suppressed the mTORC1 pathway, thereby attenuating TLR ligand\u2010induced responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TLR ligand\u2010induced activation and pro\u2010inflammatory functions of LSECs critically depend on glycolysis via the mTORC1 signalling pathway. This reveals a key metabolic mechanism underlying LSEC immune regulation during innate stimulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70864","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:03:33Z","timestamp":1788530613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycolysis Drives\n                    <scp>TLR<\/scp>\n                    Ligand\u2010Induced Maturation and Immune Activation of Liver Sinusoidal Endothelial Cells"],"prefix":"10.1111","volume":"46","author":[{"given":"Yiwen","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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Infectious Diseases and Immunity, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Littwitz\u2010Salomon","sequence":"additional","affiliation":[{"name":"Institute for the Research on HIV and AIDS\u2010Associated Diseases University Hospital of Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8262-4997","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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