دورية أكاديمية
Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal.
| العنوان: | Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal. |
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| المؤلفون: | Svensson MND; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Zoccheddu M; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Yang S; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Nygaard G; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Secchi C; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.; Department of Biomedical Sciences, National Institute of Biostructures and Biosystems, University of Sassari Medical School, 07100 Sassari, Italy., Doody KM; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Slowikowski K; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Partners HealthCare Personalized Medicine, Boston, MA 02115, USA.; Program in Medical and Population Genetics, Broad Institute of Massachusetts Technical Institute and Harvard University, Cambridge, MA 02138, USA.; Bioinformatics and Integrative Genomics, Harvard University, Cambridge, MA 02138, USA., Mizoguchi F; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan., Humby F; Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK., Hands R; Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK., Santelli E; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Sacchetti C; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Wakabayashi K; Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Wu DJ; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Barback C; Department of Radiology, University of California, La Jolla, CA 92093, USA.; UCSD Molecular Imaging Program, University of California, La Jolla, CA 92093, USA., Ai R; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA., Wang W; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA., Sims GP; Respiratory, Inflammation and Autoimmunity, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA., Mydel P; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th Floor, 5021 Bergen, Norway.; Department of Microbiology, Jagiellonian University, Kraków, Poland., Kasama T; Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Boyle DL; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Galimi F; Department of Biomedical Sciences, National Institute of Biostructures and Biosystems, University of Sassari Medical School, 07100 Sassari, Italy., Vera D; Department of Radiology, University of California, La Jolla, CA 92093, USA.; UCSD Molecular Imaging Program, University of California, La Jolla, CA 92093, USA., Tremblay ML; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal, Québec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada.; Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada., Raychaudhuri S; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Partners HealthCare Personalized Medicine, Boston, MA 02115, USA.; Program in Medical and Population Genetics, Broad Institute of Massachusetts Technical Institute and Harvard University, Cambridge, MA 02138, USA.; Rheumatology Unit, Karolinska Institutet, Stockholm S-171 76, Sweden.; Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PT, UK., Brenner MB; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Firestein GS; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA., Pitzalis C; Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK., Ekwall AH; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Centre for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Stanford SM; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Bottini N; Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.; Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. |
| المصدر: | Science advances [Sci Adv] 2020 Jun 26; Vol. 6 (26), pp. eaba4353. Date of Electronic Publication: 2020 Jun 26 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: eCollection Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| مواضيع طبية MeSH: | Antirheumatic Agents*/therapeutic use , Arthritis, Rheumatoid* , Synoviocytes*/metabolism , Synoviocytes*/pathology, Animals ; Cells, Cultured ; Fibroblasts/metabolism ; Mice ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | 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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).) |
| التعليقات: | Comment in: Nat Rev Rheumatol. 2020 Sep;16(9):473. (PMID: 32737429) |
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| معلومات مُعتمدة: | P30 AR073761 United States AR NIAMS NIH HHS; T32 AR064194 United States AR NIAMS NIH HHS; T32 HG002295 United States HG NHGRI NIH HHS; R01 AR066053 United States AR NIAMS NIH HHS; G0800648 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | 0 (Antirheumatic Agents) 0 (Tumor Necrosis Factor-alpha) |
| تواريخ الأحداث: | Date Created: 20200709 Date Completed: 20220411 Latest Revision: 20220411 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7319753 |
| DOI: | 10.1126/sciadv.aba4353 |
| PMID: | 32637608 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2375-2548 |
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| DOI: | 10.1126/sciadv.aba4353 |