{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:38:09Z","timestamp":1790678289119,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"funder":[{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine","doi-asserted-by":"crossref","award":["26-109"],"award-info":[{"award-number":["26-109"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Health, Labor, and Welfare of Japan"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Indoleamine\u20102, 3\u2010dioxygenase (IDO), an interferon\u2010\u03b3\u2010inducible enzyme catalyzing tryptophan into kynurenine, exerts dual functions in infectious diseases, acting as a suppressor of intracellular pathogens and as an immune regulator. We explored the roles of IDO in hepatitis B virus (HBV) clearance from infected patients. We examined IDO activity, serum chemokines, and cytokines in 53 HBV\u2010positive patients (25 acute hepatitis, 14 chronic hepatitis, and 14 hepatic flare) and 14 healthy volunteers. In order to clarify the mechanisms of IDO induction and its impact on HBV replication, we used a culture model consisting of human natural killer cells, plasmacytoid dendritic cells, and HBV\u2010transfected Huh7 cells in which IDO expression is controlled. A robust activation of IDO with an inverse correlation of alanine aminotransferase at the peak was observed in patients with acute hepatitis B but not in patients with hepatic flare. In acute hepatitis patients who eventually cleared HBV, IDO activity, chemokine (C\u2010X\u2010C motif) ligand 9 (CXCL9), CXCL10, and CXCL11 increased at the peak of alanine aminotransferase. In contrast, in patients with hepatic flare, IDO activity remained at lower levels during the observation period, regardless of the surge of CXCL9, CXCL10, and CXCL11 at the alanine aminotransferase peak. Natural killer cells and plasmacytoid dendritic cells synergistically produced interferon\u2010\u03b3 and interferon\u2010\u03b1, thereby enhancing IDO activity and HBV suppression in Huh7 cells. Such suppressor capacity of IDO on HBV was abrogated in IDO\u2010knockout cells and recovered by the reinduction of IDO in the cells. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> IDO is an anti\u2010HBV effector and an indicator of subsequent immune responses operative during the early phase of infection; its activity is boosted by coexisting natural killer cells and plasmacytoid dendritic cells. (H<jats:sc>epatology<\/jats:sc> 2016;63:83\u201394)<\/jats:p>","DOI":"10.1002\/hep.28282","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T14:14:35Z","timestamp":1444745675000},"page":"83-94","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":45,"title":["Indoleamine\u20102,3\u2010dioxygenase as an effector and an indicator of protective immune responses in patients with acute hepatitis B"],"prefix":"10.1097","volume":"63","author":[{"given":"Sachiyo","family":"Yoshio","sequence":"first","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Shoji","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Mano","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Mita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, National Hospital Organization,Osaka National Hospital,Chuo\u2010ku,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Research Institute for Microbial Diseases,Osaka University,Suita,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiharu","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Research Institute for Microbial Diseases,Osaka University,Suita,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alato","family":"Okuno","sequence":"additional","affiliation":[{"name":"The National Center for Geriatrics and Gerontology,Aichi,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Takikawa","sequence":"additional","affiliation":[{"name":"The National Center for Geriatrics and Gerontology,Aichi,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Mizokami","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Kanto","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,11,23]]},"reference":[{"key":"hep28282-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/S0140-6736(14)60220-8","article-title":"Hepatitis B virus infection","volume":"384","year":"2014","journal-title":"Lancet"},{"key":"hep28282-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cgh.2013.04.036","article-title":"Management of hepatitis B: our practice and how it relates to the guidelines","volume":"12","year":"2014","journal-title":"Clin Gastroenterol 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