{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:58:55Z","timestamp":1791885535461,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T00:00:00Z","timestamp":1554422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570510"],"award-info":[{"award-number":["81570510"]}],"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":["81870399"],"award-info":[{"award-number":["81870399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The liver is a central immunologic organ with a high density of myeloid and lymphoid immune cells that play important roles in the development and progression of nonalcoholic steatohepatitis (NASH). However, the immune\u2010cell\u2013mediated regulation of NASH and its underlying mechanisms remain obscure. In this study,\n                    <jats:italic>\n                      Prf1\n                      <jats:sup>null<\/jats:sup>\n                    <\/jats:italic>\n                    mice showed significantly higher plasma alanine transaminase levels, with increased liver fat accumulation, lobular inflammation, and focal necrosis compared with wild\u2010type (WT) mice after 4 wk of feeding on a methionine\u2010 and choline\u2010deficient diet (MCD) or 16 wk of feeding on a high\u2010fat diet. Perforin deficiency promoted the M1 polarization of infiltrated monocytes. Moreover, MCD\u2010fed\n                    <jats:italic>\n                      Prf1\n                      <jats:sup>null<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited increased accumulation, survival, activation, and proinflammatory cytokine production of CD8 T cells but not NK cells or CD4 T cells. Adoptive transfer of CD8 T cells or NK cells from WT or\n                    <jats:italic>\n                      Prf1\n                      <jats:sup>null<\/jats:sup>\n                    <\/jats:italic>\n                    mice, together with non\u2010CD8 cells or non\u2010NK cells from WT mice, indicated that CD8 T\u2010cell\u2013derived perforin participates in the mechanism regulating liver inflammation and thus plays a protective role in the development of NASH. Perforin\u2010deficient CD8 T cells exhibited decreased cytotoxicity toward bone marrow\u2010derived M1 monocytes and macrophages. According to the RNA sequencing data, the perforin deficiency inhibited cell apoptosis and enhanced the activation, migration, and proinflammatory cytokine production of CD8 T cells in mice with NASH. Furthermore, we found higher plasma soluble perforin levels and hepatic perforin expression in NASH patients, suggesting clinical relevance of the findings. We have elucidated an important role for the cytotoxic immune effector molecule perforin from CD8 T cells in restricting hepatic inflammation in mice with NASH and suggest that therapies designed to maximize the function of endogenous perforin in CD8 T cells might have potential benefits as NASH treatments.\u2014Wang, T., Sun, G., Wang, Y., Li, S., Zhao, X., Zhang, C., Jin, H., Tian, D., Liu, K., Shi, W., Tian, Y., Zhang, D. The immunoregulatory effects of CD8 T\u2010cell\u2013derived perforin on diet\u2010induced nonalcoholic steatohepatitis. FASEB J. 33, 8490\u20138503 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802534rr","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T16:21:28Z","timestamp":1554481288000},"page":"8490-8503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The immunoregulatory effects of CD8 T\u2010cell\u2013derived perforin on diet\u2010induced nonalcoholic steatohepatitis"],"prefix":"10.1096","volume":"33","author":[{"given":"Tianqi","family":"Wang","sequence":"first","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyong","family":"Sun","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Wang","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxiang","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Digestive Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Digestive Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunpan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Jin","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tian","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Liu","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Shi","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tian","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"Beijing Clinical Research Institute  Beijing China"},{"name":"Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Capital Medical University  Beijing China"},{"name":"General Surgery Department Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Beijing 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