Liposomal AntagomiR-155-5p Restores Anti-Inflammatory Macrophages and Improves Arthritis in Preclinical Models of Rheumatoid Arthritis.

Autor: Paoletti A; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France., Ly B; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France., Cailleau C; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., Gao F; Division of Biomedical Engineering, James Watt School of Engineering, University of Glasgow, Glasgow, United Kingdom., de Ponfilly-Sotier MP; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France., Pascaud J; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France., Rivière E; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France., Yang L; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom., Nwosu L; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom., Elmesmari A; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom., Reynaud F; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., Hita M; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., Paterson D; Division of Biomedical Engineering, James Watt School of Engineering, University of Glasgow, Glasgow, United Kingdom., Reboud J; Division of Biomedical Engineering, James Watt School of Engineering, University of Glasgow, Glasgow, United Kingdom., Fay F; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., Nocturne G; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France.; Rheumatology Department, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Le Kremlin Bicêtre, France., Tsapis N; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., McInnes IB; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom., Kurowska-Stolarska M; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom., Fattal E; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France., Mariette X; Paris-Saclay University, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France.; Rheumatology Department, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Le Kremlin Bicêtre, France.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Jan; Vol. 76 (1), pp. 18-31. Date of Electronic Publication: 2023 Nov 21.
DOI: 10.1002/art.42665
Abstrakt: Objective: We previously reported an increased expression of microRNA-155 (miR-155) in the blood monocytes of patients with rheumatoid arthritis (RA) that could be responsible for impaired monocyte polarization to anti-inflammatory M2-like macrophages. In this study, we employed two preclinical models of RA, collagen-induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR-155-5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti-inflammatory M2 phenotype.
Methods: AntagomiR-155-5p or antagomiR-control were encapsulated in PEG liposomes of 100 nm in size and -10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 μL PEG liposomes containing antagomiR-155-5p or control after the induction of arthritis.
Results: We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR-control or the systemic delivery of free antagomiR-155-5p. Moreover, treatment with PEG liposomes containing antagomiR-155-5p led to the restoration of bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells.
Conclusion: The injection of antagomiR-155-5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
Externí odkaz: