dc.contributor.author | Svensson, Mattias N.D. | |
dc.contributor.author | Zoccheddu, Martina | |
dc.contributor.author | Yang, Shen | |
dc.contributor.author | Nygaard, Gyrid | |
dc.contributor.author | Secchi, Christian | |
dc.contributor.author | Doody, Karen M. | |
dc.contributor.author | Slowikowski, Kamil | |
dc.contributor.author | Mizoguchi, Fumitaka | |
dc.contributor.author | Humby, Frances | |
dc.contributor.author | Hands, Rebecca | |
dc.contributor.author | Santelli, Eugenio | |
dc.contributor.author | Sacchetti, Cristiano | |
dc.contributor.author | Wakabayashi, Kuninobu | |
dc.contributor.author | Wu, Dennis J. | |
dc.contributor.author | Barback, Christopher | |
dc.contributor.author | Ai, Rizi | |
dc.contributor.author | Wang, Wei | |
dc.contributor.author | Sims, Gary P. | |
dc.contributor.author | Mydel, Piotr Mateusz | |
dc.contributor.author | Kasama, Tsuyoshi | |
dc.contributor.author | Boyle, David L. | |
dc.contributor.author | Galimi, Francesco | |
dc.contributor.author | Vera, David | |
dc.contributor.author | Tremblay, Michel L. | |
dc.contributor.author | Raychaudhuri, Soumya | |
dc.contributor.author | Brenner, Michael B. | |
dc.contributor.author | Firestein, Gary S. | |
dc.contributor.author | Pitzalis, Costantino | |
dc.contributor.author | Ekwall, Anna-Karin H. | |
dc.contributor.author | Stanford, Stephanie M. | |
dc.contributor.author | Bottini, Nunzio | |
dc.date.accessioned | 2021-05-18T13:15:39Z | |
dc.date.available | 2021-05-18T13:15:39Z | |
dc.date.created | 2020-09-16T14:08:25Z | |
dc.date.issued | 2020 | |
dc.Published | Science Advances. 2020, 6:eaba4353 (26), 1-18. | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | https://hdl.handle.net/11250/2755518 | |
dc.description.abstract | Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1 and 2 (Ig1&2), a decoy protein that activates the receptor tyrosine phosphatase sigma (PTPRS) on FLS, for RA therapy. We report that PTPRS expression is enriched in synovial lining RA FLS and that Ig1&2 reduces migration of RA but not osteoarthritis FLS. Administration of an Fc-fusion Ig1&2 attenuated arthritis in mice without affecting innate or adaptive immunity. Furthermore, PTPRS was down-regulated in FLS by tumor necrosis factor (TNF) via a phosphatidylinositol 3-kinase–mediated pathway, and TNF inhibition enhanced PTPRS expression in arthritic joints. Combination of ineffective doses of TNF inhibitor and Fc-Ig1&2 reversed arthritis in mice, providing an example of synergy between FLS-targeted and immunosuppressive DMARD therapies. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | AAAS | en_US |
dc.rights | Navngivelse-Ikkekommersiell 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/deed.no | * |
dc.title | Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2020 The Authors. | en_US |
dc.source.articlenumber | eaba4353 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1126/sciadv.aba4353 | |
dc.identifier.cristin | 1830490 | |
dc.source.journal | Science Advances | en_US |
dc.source.40 | 6:eaba4353 | |
dc.source.14 | 26 | |
dc.identifier.citation | Science Advances. 2020, 6 (26), eaba4353 | en_US |
dc.source.volume | 6 | en_US |
dc.source.issue | 26 | en_US |