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Synoviocyte-targete...
Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal.
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Svensson, Mattias N D (author)
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Zoccheddu, Martina (author)
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Yang, Shen (author)
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Nygaard, Gyrid (author)
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Secchi, Christian (author)
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Doody, Karen M (author)
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Slowikowski, Kamil (author)
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Mizoguchi, Fumitaka (author)
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Humby, Frances (author)
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Hands, Rebecca (author)
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Santelli, Eugenio (author)
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Sacchetti, Cristiano (author)
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Wakabayashi, Kuninobu (author)
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Wu, Dennis J (author)
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Barback, Christopher (author)
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Ai, Rizi (author)
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Wang, Wei (author)
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Sims, Gary P (author)
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Mydel, Piotr (author)
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Kasama, Tsuyoshi (author)
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Boyle, David L (author)
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Galimi, Francesco (author)
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Vera, David (author)
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Tremblay, Michel L (author)
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Raychaudhuri, Soumya (author)
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Brenner, Michael B (author)
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Firestein, Gary S (author)
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Pitzalis, Costantino (author)
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- Ekwall, Anna-Karin H (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Stanford, Stephanie M (author)
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Bottini, Nunzio (author)
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2020
- 2020
- English.
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In: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:26
- Related links:
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https://www.science....
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Animals
- Antirheumatic Agents
- therapeutic use
- Arthritis
- Rheumatoid
- Cells
- Cultured
- Fibroblasts
- metabolism
- Mice
- Synoviocytes
- metabolism
- pathology
- Tumor Necrosis Factor-alpha
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Svensson, Mattia ...
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Zoccheddu, Marti ...
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Yang, Shen
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Nygaard, Gyrid
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Secchi, Christia ...
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Doody, Karen M
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show more...
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Slowikowski, Kam ...
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Mizoguchi, Fumit ...
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Humby, Frances
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Hands, Rebecca
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Santelli, Eugeni ...
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Sacchetti, Crist ...
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Wakabayashi, Kun ...
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Wu, Dennis J
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Barback, Christo ...
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Ai, Rizi
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Wang, Wei
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Sims, Gary P
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Mydel, Piotr
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Kasama, Tsuyoshi
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Boyle, David L
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Galimi, Francesc ...
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Vera, David
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Tremblay, Michel ...
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Raychaudhuri, So ...
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Brenner, Michael ...
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Firestein, Gary ...
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Pitzalis, Costan ...
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Ekwall, Anna-Kar ...
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Stanford, Stepha ...
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Bottini, Nunzio
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Science advances
- By the university
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University of Gothenburg
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Karolinska Institutet