{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T04:40:51Z","timestamp":1770093651433,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,2,1]],"date-time":"2003-02-01T00:00:00Z","timestamp":1044057600000},"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":[[2003,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TNF-\u03b1 is a central mediator of T cell activation-induced hepatitis in mice, e.g., induced by Pseudomonas exotoxin A (PEA). In this in vivo mouse model of T cell-dependent hepatitis, liver injury depends on both TNFRs. Whereas TNFR1 can directly mediate hepatocyte death, the in vivo functions of TNFR2 in pathophysiology remained unclear. TNFR2 has been implicated in deleterious leukocyte activation in a transgenic mouse model and in enhancement of TNFR1-mediated cell death in cell lines. In this study, we clarify the role of hepatocyte- vs leukocyte-expressed TNFR2 in T cell-dependent liver injury in vivo, using the PEA-induced hepatitis model. Several types of TNFR2-expressing leukocytes, especially neutrophils and NK cells, accumulated within the liver throughout the pathogenic process. Surprisingly, only parenchymal TNFR2 expression, but not the TNFR2 expression on leukocytes, contributed to PEA-induced hepatitis, as shown by analysis of wild-type \u2192 tnfr2\u00b0 and the reciprocal mouse bone marrow chimeras. Furthermore, PEA induced NF-\u03baB activation and cytokine production in the livers of both wild-type and tnfr2\u00b0 mice, whereas only primary mouse hepatocytes from wild-type, but not from tnfr2\u00b0, mice were susceptible to cell death induced by a combination of agonistic anti-TNFR1 and anti-TNFR2 Abs. Our results suggest that parenchymal, but not leukocyte, TNFR2 mediates T cell-dependent hepatitis in vivo. The activation of leukocytes does not appear to be disturbed by the absence of TNFR2.<\/jats:p>","DOI":"10.4049\/jimmunol.170.4.2129","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:49:07Z","timestamp":1398109747000},"page":"2129-2137","source":"Crossref","is-referenced-by-count":14,"title":["Parenchymal, But Not Leukocyte, TNF Receptor 2 Mediates T Cell-Dependent Hepatitis in Mice"],"prefix":"10.1093","volume":"170","author":[{"given":"Jens","family":"Schu\u0308mann","sequence":"first","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Mu\u0308hlen","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra K","family":"Kiemer","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology, University of Mu\u0308nchen , Mu\u0308nchen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika M","family":"Vollmar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology, University of Mu\u0308nchen , Mu\u0308nchen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisa","family":"Tiegs","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,2,15]]},"reference":[{"key":"2026020210113850300_R1","first-page":"3666","volume-title":"Proc. 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