{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:35:37Z","timestamp":1790379337205,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":1351,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["li.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Laboratory Investigation"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1038\/s41374-018-0184-7","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T08:03:34Z","timestamp":1548317014000},"page":"648-658","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"title":["FOXO3 is involved in the tumor necrosis factor-driven inflammatory response in fibroblast-like synoviocytes"],"prefix":"10.1016","volume":"99","author":[{"given":"Bernhard","family":"Brandstetter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Dalwigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Platzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Niederreiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Kartnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-7585","authenticated-orcid":false,"given":"Gregory I.","family":"Vladimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth A.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Sevelda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Holinka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Superti-Furga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef S.","family":"Smolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans P.","family":"Kiener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Karonitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/s41374-018-0184-7_bib1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"10.1038\/s41374-018-0184-7_bib2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-065X.2008.00648.x","article-title":"The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis","volume":"223","author":"Noss","year":"2008","journal-title":"Immunol Rev"},{"key":"10.1038\/s41374-018-0184-7_bib3","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nchembio.2211","article-title":"Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation","volume":"13","author":"Jones","year":"2017","journal-title":"Nat Chem Biol"},{"key":"10.1038\/s41374-018-0184-7_bib4","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.ajpath.2012.01.030","article-title":"PI3 kinase delta is a key regulator of synoviocyte function in rheumatoid arthritis","volume":"180","author":"Bartok","year":"2012","journal-title":"Am J Pathol"},{"key":"10.1038\/s41374-018-0184-7_bib5","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1096\/fj.09-135160","article-title":"PI3Kgamma regulates cartilage damage in chronic inflammatory arthritis","volume":"23","author":"Hayer","year":"2009","journal-title":"FASEB J"},{"key":"10.1038\/s41374-018-0184-7_bib6","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/1529-0131(200107)44:7<1555::AID-ART279>3.0.CO;2-M","article-title":"Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt","volume":"44","author":"Zhang","year":"2001","journal-title":"Arthritis Rheum"},{"key":"10.1038\/s41374-018-0184-7_bib7","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"10.1038\/s41374-018-0184-7_bib8","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"10.1038\/s41374-018-0184-7_bib9","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1002\/art.27504","article-title":"Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis","volume":"62","author":"Cejka","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1038\/s41374-018-0184-7_bib10","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/art.22653","article-title":"Inhibition of forkhead box class O family member transcription factors in rheumatoid synovial tissue","volume":"56","author":"Ludikhuize","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1038\/s41374-018-0184-7_bib11","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/nm1284","article-title":"Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis","volume":"11","author":"Camps","year":"2005","journal-title":"Nat Med"},{"key":"10.1038\/s41374-018-0184-7_bib12","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/eji.200838266","article-title":"Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils","volume":"38","author":"Randis","year":"2008","journal-title":"Eur J Immunol"},{"key":"10.1038\/s41374-018-0184-7_bib13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrm3507","article-title":"FOXOs: signalling integrators for homeostasis maintenance","volume":"14","author":"Eijkelenboom","year":"2013","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1038\/s41374-018-0184-7_bib14","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/art.39760","article-title":"Association between genetic variation in FOXO3 and reductions in inflammation and disease activity in inflammatory polyarthritis","volume":"68","author":"Viatte","year":"2016","journal-title":"Arthritis Rheum"},{"key":"10.1038\/s41374-018-0184-7_bib15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cell.2013.08.034","article-title":"Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway","volume":"155","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"10.1038\/s41374-018-0184-7_bib16","first-page":"1009","article-title":"Rheumatoid arthritis complicating adjuvant interferon-alpha therapy for malignant melanoma","volume":"26","author":"Johnson","year":"1999","journal-title":"J Rheumatol"},{"key":"10.1038\/s41374-018-0184-7_bib17","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1038\/s41374-018-0184-7_bib18","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.2353\/ajpath.2006.050999","article-title":"Cadherin-11 induces rheumatoid arthritis fibroblast-like synoviocytes to form lining layers in vitro","volume":"168","author":"Kiener","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1038\/s41374-018-0184-7_bib19","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nprot.2010.74","article-title":"Efficient siRNA-mediated prolonged gene silencing in human amniotic fluid stem cells","volume":"5","author":"Rosner","year":"2010","journal-title":"Nat Protoc"},{"key":"10.1038\/s41374-018-0184-7_bib20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1038\/s41374-018-0184-7_bib21","doi-asserted-by":"crossref","first-page":"e1003118","DOI":"10.1371\/journal.pcbi.1003118","article-title":"Software for computing and annotating genomic ranges","volume":"9","author":"Lawrence","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"10.1038\/s41374-018-0184-7_bib22","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"10.1038\/s41374-018-0184-7_bib23","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nbt.2450","article-title":"Differential analysis of gene regulation at transcript resolution with RNA-seq","volume":"31","author":"Trapnell","year":"2013","journal-title":"Nat Biotechnol"},{"key":"10.1038\/s41374-018-0184-7_bib24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1038\/s41374-018-0184-7_bib25","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/bioinformatics\/btn615","article-title":"AmiGO: online access to ontology and annotation data","volume":"25","author":"Carbon","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1038\/s41374-018-0184-7_bib26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"10.1038\/s41374-018-0184-7_bib27","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.celrep.2018.04.044","article-title":"mTOR senses environmental cues to shape the fibroblast-like synoviocyte response to inflammation","volume":"23","author":"Karonitsch","year":"2018","journal-title":"Cell Rep"},{"key":"10.1038\/s41374-018-0184-7_bib28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1535-6108(02)00086-7","article-title":"A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR","volume":"2","author":"Ramaswamy","year":"2002","journal-title":"Cancer Cell"},{"key":"10.1038\/s41374-018-0184-7_bib29","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nature11428","article-title":"A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses","volume":"490","author":"Litvak","year":"2012","journal-title":"Nature"},{"key":"10.1038\/s41374-018-0184-7_bib30","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/ard.2011.150284","article-title":"The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon","volume":"71","author":"Rosengren","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"10.1038\/s41374-018-0184-7_bib31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbrc.2007.04.096","article-title":"PI3K is negatively regulated by PIK3IP1, a novel p110 interacting protein","volume":"358","author":"Zhu","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1038\/s41374-018-0184-7_bib32","doi-asserted-by":"crossref","first-page":"4990","DOI":"10.1096\/fj.12-208587","article-title":"Expression of constitutively active FoxO3 in murine forebrain leads to a loss of neural progenitors","volume":"26","author":"Schmidt-Strassburger","year":"2012","journal-title":"FASEB J"},{"key":"10.1038\/s41374-018-0184-7_bib33","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/labinvest.2009.66","article-title":"Tumor suppressor FOXO3 participates in the regulation of intestinal inflammation","volume":"89","author":"Snoeks","year":"2009","journal-title":"Lab Invest"},{"key":"10.1038\/s41374-018-0184-7_bib34","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/ard.2009.109991","article-title":"FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue","volume":"69","author":"Turrel-Davin","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"10.1038\/s41374-018-0184-7_bib35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.immuni.2004.06.016","article-title":"Regulation of NF-kappaB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a","volume":"21","author":"Lin","year":"2004","journal-title":"Immunity"},{"key":"10.1038\/s41374-018-0184-7_bib36","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nm1248","article-title":"Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis","volume":"11","author":"Jonsson","year":"2005","journal-title":"Nat Med"},{"key":"10.1038\/s41374-018-0184-7_bib37","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.imlet.2011.02.010","article-title":"Why does chronic inflammation persist: aan unexpected role for fibroblasts","volume":"138","author":"Buckley","year":"2011","journal-title":"Immunol Lett"},{"key":"10.1038\/s41374-018-0184-7_bib38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1006\/clim.2000.4957","article-title":"CXCR3 and CCR5 ligands in rheumatoid arthritis synovium","volume":"98","author":"Patel","year":"2001","journal-title":"Clin Immunol"},{"key":"10.1038\/s41374-018-0184-7_bib39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1365-2249.2007.03363.x","article-title":"Glucocorticoid-induced tumour necrosis factor receptor-related protein-mediated macrophage stimulation may induce cellular adhesion and cytokine expression in rheumatoid arthritis","volume":"148","author":"Bae","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"10.1038\/s41374-018-0184-7_bib40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00296-004-0449-x","article-title":"The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis","volume":"25","author":"Ueno","year":"2005","journal-title":"Rheumatol Int"},{"key":"10.1038\/s41374-018-0184-7_bib41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3109\/03009742.2011.623137","article-title":"Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5","volume":"41","author":"Yoshida","year":"2012","journal-title":"Scand J Rheumatol"},{"key":"10.1038\/s41374-018-0184-7_bib42","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.autrev.2012.10.001","article-title":"The interaction between CXCL10 and cytokines in chronic inflammatory arthritis","volume":"12","author":"Lee","year":"2013","journal-title":"Autoimmun Rev"},{"key":"10.1038\/s41374-018-0184-7_bib43","doi-asserted-by":"crossref","first-page":"15059","DOI":"10.1073\/pnas.2334901100","article-title":"Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells","volume":"100","author":"Tone","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/s41374-018-0184-7_bib44","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1158\/0008-5472.CAN-08-0025","article-title":"PIK3IP1, a negative regulator of PI3K, suppresses the development of hepatocellular carcinoma","volume":"68","author":"He","year":"2008","journal-title":"Cancer Res"},{"key":"10.1038\/s41374-018-0184-7_bib45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/ng.2846","article-title":"Inactivating CUX1 mutations promote tumorigenesis","volume":"46","author":"Wong","year":"2014","journal-title":"Nat Genet"},{"key":"10.1038\/s41374-018-0184-7_bib46","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.4049\/jimmunol.1501896","article-title":"Cutting edge: Foxp1 controls naive CD8+T cell quiescence by simultaneously repressing key pathways in cellular metabolism and cell cycle progression","volume":"196","author":"Wei","year":"2016","journal-title":"J Immunol"},{"key":"10.1038\/s41374-018-0184-7_bib47","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1002\/eji.201141653","article-title":"Inhibition of T-cell activation by PIK3IP1","volume":"42","author":"DeFrances","year":"2012","journal-title":"Eur J Immunol"}],"container-title":["Laboratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0184-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0184-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722026204?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722026204?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0184-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T19:50:02Z","timestamp":1758397802000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0023683722026204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["S0023683722026204"],"URL":"https:\/\/doi.org\/10.1038\/s41374-018-0184-7","relation":{},"ISSN":["0023-6837"],"issn-type":[{"value":"0023-6837","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"FOXO3 is involved in the tumor necrosis factor-driven inflammatory response in fibroblast-like synoviocytes","name":"articletitle","label":"Article Title"},{"value":"Laboratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/s41374-018-0184-7","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 United States & Canadian Academy of Pathology.","name":"copyright","label":"Copyright"}]}}