{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T11:21:35Z","timestamp":1777116095408,"version":"3.51.4"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T00:00:00Z","timestamp":1493856000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T00:00:00Z","timestamp":1493856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Toll\u2010like receptor\u20105 (TLR5) signaling regulates the immune privileged status of the liver and is involved in hepatic immune disorders. However, the role of TLR5 has not yet been investigated in experimental models of concanavalin A (Con A)\u2013mediated liver injury. Here, we show that TLR5 is highly up\u2010regulated in the hepatic mononuclear cells of mice during Con A\u2013induced hepatitis. Increased mortality and liver histopathology of TLR5\u2010deficient mice correlated with excessive production of proinflammatory cytokines, suggesting that TLR5 knockout mice were more susceptible to Con A\u2013induced hepatitis. We also report that administration of CBLB502, an exogenous TLR5 agonist, substantially alleviated Con A\u2013mediated hepatitis in wild\u2010type mice as shown by increased survival rates, reduced aminotransferase and proinflammatory cytokine production, impaired lymphocyte infiltration, and ameliorated hepatocyte necrosis and\/or apoptosis. Mechanistic studies revealed that CBLB502 acts as a negative regulator in limiting T\u2010cell\/natural killer T\u2010cell activity and cytokine production in the Con A\u2013hepatitis model. Bone marrow transplantation experiments showed that TLR5 in bone marrow\u2013derived cells contributed to the hepatoprotective efficacy of CBLB502 against Con A\u2013induced liver injury. Moreover, interleukin\u20106 elevation induced by CBLB502 is an important protective factor against Con A\u2013induced liver injury. In addition, we demonstrate that CBLB502 suppresses \u03b1\u2010galactosylceramide\u2010induced natural killer T cell\u2013dependent inflammatory liver injury. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: The TLR5 signaling pathway plays an important role in T cell\u2013mediated hepatic injury and may be exploited for therapeutic treatment of inflammatory liver diseases. (H<jats:sc>epatology<\/jats:sc> 2017;65:2059\u20102073).<\/jats:p>","DOI":"10.1002\/hep.29140","type":"journal-article","created":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T17:26:42Z","timestamp":1488994002000},"page":"2059-2073","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Toll\u2010like receptor 5 signaling restrains T\u2010cell\/natural killer T\u2010cell activation and protects against concanavalin A\u2013induced hepatic injury"],"prefix":"10.1097","volume":"65","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering,Tianjin University,Tianjin,China"},{"name":"Beijing Institute of Radiation Medicine,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering,Tianjin University,Tianjin,China"},{"name":"Beijing Institute of Radiation Medicine,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Hui","family":"Ge","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong\u2010Hua","family":"Yin","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Qun","family":"Zhan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine,Beijing,China"},{"name":"State Key Laboratory of Proteomics,Beijing,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Qiang","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering,Tianjin 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