{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:32:21Z","timestamp":1792225941323,"version":"4.4.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,2,18]]},"abstract":"<jats:p>Tumor necrosis factor (TNF) is key to the pathogenesis of various arthritic diseases and inflammatory bowel disease (IBD). Anti-TNF therapies have proved successful in the clinical treatment of these diseases, but a mechanistic understanding of TNF function is still lacking. We have investigated early cellular mechanisms of TNF function in these diseases using an established TNF transgenic model, which develops a spondyloarthritis-like disease characterized by peripheral joint arthritis, sacroiliitis, enthesitis, and Crohn's-like IBD. Bone marrow grafting experiments demonstrated that development of arthritis requires TNF receptor I (TNFRI) expression in the radiation-resistant compartment, which is also known to be a sufficient target of TNF in the development of Crohn's-like IBD in the same model. Early activation of synovial fibroblasts and intestinal myofibroblasts could also be demonstrated by perturbed expression of matrix metalloproteases and their inhibitors. Notably, selective Cre\/loxP-mediated TNFRI expression in mesenchymal cells resulted in a fully arthritic\u2013spondyloarthritic and intestinal phenotype, indicating that mesenchymal cells are primary and sufficient targets of TNF in these pathologies. Our results offer a novel mechanistic perspective for TNF function in gut and joint pathologies and indicate early common cellular pathways that may also explain the often observed synovial\u2013gut axis in human disease.<\/jats:p>","DOI":"10.1084\/jem.20070906","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T20:47:26Z","timestamp":1202158046000},"page":"331-337","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":313,"title":["Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases"],"prefix":"10.1084","volume":"205","author":[{"given":"Maria","family":"Armaka","sequence":"first","affiliation":[{"name":"1Institute of Immunology, Biomedical Sciences Research Center (BSRC) \u201cAlexander Fleming,\u201d Vari 16672, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Apostolaki","sequence":"additional","affiliation":[{"name":"1Institute of Immunology, Biomedical Sciences Research Center (BSRC) \u201cAlexander Fleming,\u201d Vari 16672, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Jacques","sequence":"additional","affiliation":[{"name":"2Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris L.","family":"Kontoyiannis","sequence":"additional","affiliation":[{"name":"1Institute of Immunology, Biomedical Sciences Research Center (BSRC) \u201cAlexander Fleming,\u201d Vari 16672, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Elewaut","sequence":"additional","affiliation":[{"name":"2Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kollias","sequence":"additional","affiliation":[{"name":"1Institute of Immunology, Biomedical Sciences Research Center (BSRC) \u201cAlexander Fleming,\u201d Vari 16672, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,2,4]]},"reference":[{"key":"2023072915335102800_BIB1","first-page":"95","volume":"27","year":"1988","journal-title":"Br. J. Rheumatol."},{"key":"2023072915335102800_BIB2","first-page":"2273","volume":"22","year":"1995","journal-title":"J. Rheumatol."},{"key":"2023072915335102800_BIB3","first-page":"2860","volume":"27","year":"2000","journal-title":"J. Rheumatol."},{"key":"2023072915335102800_BIB4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.7326\/0003-4819-136-12-200206180-00011","volume":"136","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"2023072915335102800_BIB5","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature03727","volume":"435","year":"2005","journal-title":"Nature."},{"key":"2023072915335102800_BIB6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nrd2196","volume":"6","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023072915335102800_BIB7","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1002\/j.1460-2075.1991.tb04978.x","volume":"10","year":"1991","journal-title":"EMBO J."},{"key":"2023072915335102800_BIB8","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/art.20194","volume":"50","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2023072915335102800_BIB9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","volume":"10","year":"1999","journal-title":"Immunity."},{"key":"2023072915335102800_BIB10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1084\/jem.181.1.137","volume":"181","year":"1995","journal-title":"J. Exp. Med."},{"key":"2023072915335102800_BIB11","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/0092-8674(90)90512-D","volume":"63","year":"1990","journal-title":"Cell."},{"key":"2023072915335102800_BIB12","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1084\/jem.20020281","volume":"196","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072915335102800_BIB13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrd1986","volume":"5","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023072915335102800_BIB14","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0092-8674(93)90134-C","volume":"73","year":"1993","journal-title":"Cell."},{"key":"2023072915335102800_BIB15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1471-4906(01)01863-4","volume":"22","year":"2001","journal-title":"Trends Immunol."},{"key":"2023072915335102800_BIB16","doi-asserted-by":"crossref","first-page":"5968","DOI":"10.4049\/jimmunol.177.9.5968","volume":"177","year":"2006","journal-title":"J. Immunol."},{"key":"2023072915335102800_BIB17","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.coph.2004.06.005","volume":"4","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"2023072915335102800_BIB18","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/01.bor.0000231904.04548.09","volume":"18","year":"2006","journal-title":"Curr. Opin. Rheumatol."},{"key":"2023072915335102800_BIB19","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.4049\/jimmunol.160.8.4098","volume":"160","year":"1998","journal-title":"J. Immunol."},{"key":"2023072915335102800_BIB20","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1083\/jcb.135.4.1163","volume":"135","year":"1996","journal-title":"J. Cell Biol."},{"key":"2023072915335102800_BIB21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","volume":"21","year":"1999","journal-title":"Nat. Genet."},{"key":"2023072915335102800_BIB22","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<147::AID-GENE90>3.0.CO;2-G","volume":"28","year":"2000","journal-title":"Genesis."},{"key":"2023072915335102800_BIB23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.immuni.2005.11.013","volume":"24","year":"2006","journal-title":"Immunity."},{"key":"2023072915335102800_BIB24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1136\/jcp.47.2.113","volume":"47","year":"1994","journal-title":"J. Clin. Pathol."},{"key":"2023072915335102800_BIB25","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1136\/ard.62.11.1094","volume":"62","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"2023072915335102800_BIB26","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nri1418","volume":"4","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2023072915335102800_BIB27","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/art.502","volume":"46","year":"2002","journal-title":"Arthritis Rheum."},{"key":"2023072915335102800_BIB28","first-page":"1607","volume":"149","year":"1996","journal-title":"Am. J. Pathol."},{"key":"2023072915335102800_BIB29","doi-asserted-by":"crossref","first-page":"C183","DOI":"10.1152\/ajpcell.1999.277.2.C183","volume":"277","year":"1999","journal-title":"Am. J. Physiol."},{"key":"2023072915335102800_BIB30","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature05698","volume":"446","year":"2007","journal-title":"Nature."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/205\/2\/331\/1897941\/jem_20070906.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/205\/2\/331\/1897941\/jem_20070906.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T11:34:24Z","timestamp":1690630464000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/205\/2\/331\/40253\/Mesenchymal-cell-targeting-by-TNF-as-a-common"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,4]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,2,18]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20070906","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1100301.556487","asserted-by":"object"}]},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2008,2,4]]}}}