Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal.

Animals Antirheumatic Agents / therapeutic use Arthritis, Rheumatoid Cells, Cultured Fibroblasts / metabolism Mice Synoviocytes / metabolism Tumor Necrosis Factor-alpha / metabolism

Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
06 2020
Historique:
received: 03 12 2019
accepted: 20 04 2020
entrez: 9 7 2020
pubmed: 9 7 2020
medline: 12 4 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1126/sciadv.aba4353 PMID: 32637608 PMC: PMC7319753
pubmed: 32637608
doi: 10.1126/sciadv.aba4353
pii: aba4353
pmc: PMC7319753
doi:

Substances chimiques

Antirheumatic Agents 0
Tumor Necrosis Factor-alpha 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaba4353

Subventions

Organisme : NIAMS NIH HHS
ID : P30 AR073761
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR064194
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR066053
Pays : United States
Organisme : Medical Research Council
ID : G0800648
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

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).

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Auteurs

Mattias N D 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.
ORCID: 0000-0001-8077-9824

Martina Zoccheddu (M)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.

Shen Yang (S)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.
ORCID: 0000-0002-4983-6787

Gyrid Nygaard (G)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.

Christian 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.
ORCID: 0000-0001-5725-9214

Karen M Doody (KM)

Division of Cellular Biology, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Kamil 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.

Fumitaka 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.
ORCID: 0000-0002-3956-7122

Frances 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.
ORCID: 0000-0003-1280-9133

Rebecca 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.
ORCID: 0000-0002-9969-6452

Eugenio 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.
ORCID: 0000-0002-8739-2750

Cristiano 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.

Kuninobu Wakabayashi (K)

Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Dennis J Wu (DJ)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.

Christopher 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.

Rizi Ai (R)

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
ORCID: 0000-0002-1605-7533

Wei Wang (W)

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
ORCID: 0000-0003-4377-5060

Gary P Sims (GP)

Respiratory, Inflammation and Autoimmunity, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.

Piotr 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.
ORCID: 0000-0001-5072-9391

Tsuyoshi Kasama (T)

Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
ORCID: 0000-0002-3871-6456

David L Boyle (DL)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.
ORCID: 0000-0002-1454-2834

Francesco Galimi (F)

Department of Biomedical Sciences, National Institute of Biostructures and Biosystems, University of Sassari Medical School, 07100 Sassari, Italy.
ORCID: 0000-0002-7391-0596

David 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.
ORCID: 0000-0001-8253-1099

Michel L 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.

Soumya 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.
ORCID: 0000-0002-1901-8265

Michael B Brenner (MB)

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0001-6202-8445

Gary S Firestein (GS)

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.
ORCID: 0000-0003-3495-960X

Costantino 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.
ORCID: 0000-0003-1326-5051

Anna-Karin H 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.
ORCID: 0000-0001-8236-6089

Stephanie M 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.

Nunzio 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.
ORCID: 0000-0001-9025-7501

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antirhumatismaux › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Polyarthrite rhumatoïde › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Cellules › Cellules cultivées › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Cellules synoviales › Synoviocyte-targeted therapy synergizes with...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Synoviocyte-targeted therapy synergizes with...