{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:44:55Z","timestamp":1773693895635,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"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":[[2009,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TLR3 is known to respond to dsRNA from viruses, apoptotic cells, and\/or necrotic cells. Dying cells are a rich source of ligands that can activate TLRs, such as TLR3. TLR3 expressed in the liver is likely to be a mediator of innate activation and inflammation in the liver. The importance of this function of TLR3 during acute hepatitis has not previously been fully explored. We used the mouse model of Con A-induced hepatitis and observed a novel role for TLR3 in hepatocyte damage in the absence of an exogenous viral stimulus. Interestingly, TLR3 expression in liver mononuclear cells and sinus endothelial cells was up-regulated after Con A injection and TLR3\u2212\/\u2212 mice were protected from Con A-induced hepatitis. Moreover, splenocytes from TLR3\u2212\/\u2212 mice proliferated less to Con A stimulation in the presence of RNA derived from damaged liver tissue compared with wild-type (WT) mice. To determine the relative contribution of TLR3 expression by hematopoietic cells or nonhematopoietic to liver damage during Con A-induced hepatitis, we generated bone marrow chimeric mice. TLR3\u2212\/\u2212 mice engrafted with WT hematopoietic cells were protected in a similar manner to WT mice reconstituted with TLR3\u2212\/\u2212 bone marrow, indicating that TLR3 signaling in both nonhematopoietic and hematopoietic cells plays an important role in mediating liver damage. In summary, our data suggest that TLR3 signaling is necessary for Con A-induced liver damage in vivo and that TLR3 regulates inflammation and the adaptive T cell immune response in the absence of viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.0901221","type":"journal-article","created":{"date-parts":[[2009,8,26]],"date-time":"2009-08-26T22:24:00Z","timestamp":1251325440000},"page":"3712-3719","source":"Crossref","is-referenced-by-count":37,"title":["Inflammatory Regulation by TLR3 in Acute Hepatitis"],"prefix":"10.1093","volume":"183","author":[{"given":"Xiaoyan","family":"Xiao","sequence":"first","affiliation":[{"name":"Section of Endocrinology, Department of Internal Medicine"},{"name":"Department of Endocrinology, Qilu Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shandong Provincial Hospital, Shandong University , Jinan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Rodriguez-Pinto","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Department of Internal Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dake","family":"Qi","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Octavian","family":"Henegariu","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Immunobiology, Yale School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Alexopoulou","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille Luminy, INSERM Unit\u00e9 631, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 6102, Universit\u00e9 de la M\u00e9diterran\u00e9e, Campus de Luminy , Case 906, Marseille,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Immunobiology, Yale School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F Susan","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Bristol, University Walk , Bristol,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wen","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Department of Internal Medicine"},{"name":"Center of Autoimmune Hepatitis, You-An Hospital, Capital University of Medicine , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,9,15]]},"reference":[{"key":"2026012811255912600_R1","first-page":"331","article-title":"Fulminant liver disease.","volume-title":"Clin. 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