{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:57:53Z","timestamp":1790506673383,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Alveolar echinococcosis (AE) is a lethal helminthic liver disease caused by persistent infection with <jats:italic toggle=\"yes\">Echinococcus multilocularis<\/jats:italic>. Although more attention has been paid to the immunotolerance of T cells caused by <jats:italic toggle=\"yes\">E<\/jats:italic>. <jats:italic toggle=\"yes\">multilocularis<\/jats:italic> infection, the role of natural killer (NK) cell, a critical player in liver immunity, is seldom studied.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Here, we observed that NK cells from the blood and closed liver tissue (CLT) of AE patients expressed a higher level of inhibitory receptor TIGIT and were functionally exhausted with a lower expression of granzyme B, perforin, interferon\u2010gamma (IFN\u2010\u03b3), and TNF\u2010\u03b1. Addition of anti\u2010TIGIT (T\u2010cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine\u2010based inhibitory motif domain) monoclonal antibody into AE patients\u2019 peripheral blood mononuclear cell culture significantly enhanced the synthesis of IFN\u2010\u03b3 and TNF\u2010\u03b1 by NK cells, indicating the reversion of exhausted NK cells by TIGIT blockade. In the mouse model of <jats:italic toggle=\"yes\">E<\/jats:italic>. <jats:italic toggle=\"yes\">multilocularis<\/jats:italic> infection, liver and splenic TIGIT<jats:sup>+<\/jats:sup> NK cells progressively increased dependent of infection dosage and timing and were less activated and less degranulated with lower cytokine secretion. Furthermore, TIGIT deficiency or blockade <jats:italic toggle=\"yes\">in vivo<\/jats:italic> inhibited liver metacestode growth, reduced liver injury, and increased the level of IFN\u2010\u03b3 produced by liver NK cells. Interestingly, NK cells from mice with persistent chronic infection expressed a higher level of TIGIT compared to self\u2010healing mice. To look further into the mechanisms, more regulatory CD56<jats:sup>bright<\/jats:sup> and murine CD49a<jats:sup>+<\/jats:sup> NK cells with higher TIGIT expression existed in livers of AE patients and mice infected with <jats:italic toggle=\"yes\">E<\/jats:italic>. <jats:italic toggle=\"yes\">multilocularis<\/jats:italic>, respectively. They coexpressed higher surface programmed death ligand 1 and secreted more IL\u201010, two strong inducers to mediate the functional exhaustion of NK cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results indicate that inhibitory receptor TIGIT is involved in NK cell exhaustion and immune escape from <jats:italic toggle=\"yes\">E<\/jats:italic>. <jats:italic toggle=\"yes\">multilocularis<\/jats:italic> infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32035","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T05:11:12Z","timestamp":1625116272000},"page":"3376-3393","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":51,"title":["Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection"],"prefix":"10.1097","volume":"74","author":[{"given":"Chuanshan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinling","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"},{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Li","sequence":"additional","affiliation":[{"name":"Basic Medical College,Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Echinococcosis,Clinical Medicine Institute,WHO Collaborating Centre for Prevention and Case Management of Echinococcosis,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chronic Disease Laboratory,Institutes for Life Sciences and School of Medicine,South China University of Technology,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Chronic Disease Laboratory,Institutes for Life Sciences and School of Medicine,South China University of Technology,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuerganaili","family":"Aji","sequence":"additional","affiliation":[{"name":"Department of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyong","family":"Lin","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Echinococcosis,Clinical Medicine Institute,WHO Collaborating Centre for Prevention and Case Management of Echinococcosis,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique A.","family":"Vuitton","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for the Prevention and Treatment of Human Echinococcosis,Department of Parasitology,University Bourgogne Franche\u2010Comt\u00e9 (EA 3181) and University Hospital,Besan\u00e7on,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Immunology,University of Science and Technology of China,Hefei,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Immunology,University of Science and Technology of China,Hefei,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,Xinjiang Medical University,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"hep32035-bib-0001-20250824","article-title":"Echinococcosis: advances in the 21st century","volume":"32","year":"2019","journal-title":"Clin Microbiol Rev"},{"key":"hep32035-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apar.2016.09.005","article-title":"Immunology of alveolar and cystic echinococcosis (AE and CE)","volume":"96","year":"2017","journal-title":"Adv 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