{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:52:22Z","timestamp":1789786342195,"version":"4.0.1"},"reference-count":29,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,4,23]]},"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Fulminant viral hepatitis (FH) remains a serious clinical problem for which the underlying pathogenesis remains unclear. The B and T lymphocyte attenuator (BTLA) is an immunoglobulin-domain-containing protein that has the capacity to maintain peripheral tolerance and limit immunopathological damage during immune responses. However, its precise role in FH has yet to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      BTLA-deficient (BTLA\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice and their wild-type littermates were infected with murine hepatitis virus strain-3 (MHV-3), and the levels of tissue damage, cell apoptosis, serum liver enzymes, fibrinogen-like protein 2 (FGL2) and cytokine production were measured and compared. Survival rate was studied after MHV-3 infection with or without adoptive transferring macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FGL2 production, liver and spleen damage, and mortality were significantly reduced in BTLA\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice infected with MHV-3. This effect is due to rapid, TRAIL (TNF-related apoptosis-inducing ligand)-dependent apoptosis of MHV-3-infected macrophages in BTLA\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. The early loss of macrophages resulted in reduced pathogenic tumour necrosis factor \u03b1 (TNF\u03b1) and FGL2 levels and lower viral titres. The importance of TNF\u03b1 in MHV-3-induced pathology was demonstrated by increased mortality in TNF\u03b1-treated MHV-3-infected BTLA\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, whereas TNF\u03b1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were resistant to the infection. Moreover, adoptively transferring macrophages to BTLA\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice caused sensitisation, whereas blocking BTLA protected wild-type mice from virus-induced FH mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BTLA promotes the pathogenesis of virus-induced FH by enhancing macrophage viability and function. Targeting BTLA may be a novel strategy for the treatment of FH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2012-302239","type":"journal-article","created":{"date-parts":[[2012,5,26]],"date-time":"2012-05-26T00:06:35Z","timestamp":1337990795000},"page":"1204-1213","source":"Crossref","is-referenced-by-count":35,"title":["Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3"],"prefix":"10.1136","volume":"62","author":[{"given":"Chengying","family":"Yang","sequence":"first","affiliation":[{"name":"Deaprtment of Basic Medicine Institute of Immunology, PLA, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Deaprtment of Basic Medicine Institute of Immunology, PLA, Third Military Medical University, Chongqing, 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