{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:57:51Z","timestamp":1790337471688,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic hepatitis B virus (HBV) infection is characterized by sustained liver inflammation with an influx of lymphocytes, which contributes to the development of cirrhosis and hepatocellular carcinoma. The mechanisms underlying this immune-mediated hepatic pathogenesis remain ill defined. We report in this article that repetitive infusion of anti-CD137 agonist mAb in HBV-transgenic mice closely mimics this process by sequentially inducing hepatitis, fibrosis, cirrhosis, and, ultimately, liver cancer. CD137 mAb initially triggers hepatic inflammatory infiltration due to activation of nonspecific CD8+ T cells with memory phenotype. CD8+ T cell-derived IFN-\u03b3 plays a central role in the progression of chronic liver diseases by actively recruiting hepatic macrophages to produce fibrosis-promoting cytokines and chemokines, including TNF-\u03b1, IL-6, and MCP-1. Importantly, the natural ligand of CD137 was upregulated significantly in circulating CD14+ monocytes in patients with chronic hepatitis B infection and closely correlated with development of liver cirrhosis. Thus, sustained CD137 stimulation may be a contributing factor for liver immunopathology in chronic HBV infection. Our studies reveal a common molecular pathway that is used to defend against viral infection but also causes chronic hepatic diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1000927","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T00:27:41Z","timestamp":1289262461000},"page":"7654-7662","source":"Crossref","is-referenced-by-count":62,"title":["CD137-Mediated Pathogenesis from Chronic Hepatitis to Hepatocellular Carcinoma in Hepatitis B Virus-Transgenic Mice"],"prefix":"10.1093","volume":"185","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]},{"name":"Graduate University, Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, The First Affiliated Hospital, Henan College of Traditional Medicine , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]},{"name":"Graduate University, Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhou","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, 301 General Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongling","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhu","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]},{"name":"Graduate University, Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicine, The First Affiliated Hospital, Henan College of Traditional Medicine , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, The First Affiliated Hospital, Henan College of Traditional Medicine , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, 301 General Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]},{"name":"Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics , Beijing ,","place":["China"]},{"name":"Graduate University, Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,15]]},"reference":[{"key":"2025032412173591000_r1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.pathol.1.110304.100230","article-title":"Immunobiology and pathogenesis of viral hepatitis","volume":"1","author":"Guidotti","year":"2006","journal-title":"Annu. 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