Liposomal AntagomiR‐155‐5p restores anti‐inflammatory macrophages and improves arthritis in pre‐clinical models of Rheumatoid arthritis
Résumé
Introduction We previously reported an increased expression of miR‐155 in rheumatoid arthritis (RA) patients blood monocytes that could be responsible for impaired monocyte polarization to anti‐inflammatory M2‐like macrophages. In this study, we employed two pre‐clinical models of RA: the Collagen‐Induce‐Arthritis (CIA) and the K/BxN Serum‐Transfer‐Arthritis (STA), to examine the therapeutic potential of antagomiR‐155‐5p entrapped within PEGylated (PEG)‐liposomes in resolution of arthritis and re‐polarization of monocytes towards anti‐inflammatory M2 phenotype. Methods AntagomiR‐155‐5p or antagomiR‐control were encapsulated in PEG‐liposomes of 100 nm in size and ‐10mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1,5nmol/100μL PEG‐liposomes containing antagomiR‐155‐5p or control after induction of arthritis. Results We demonstrated the biodistribution of fluorescently tagged‐PEG‐liposomes to inflamed joints 1 hour after injection of fluorescently tagged‐PEG‐liposomes and as well as their subsequent liver's accumulation after 48 hours, indicative of hepatic clearance, in arthritic mice. Injection of PEG‐liposomes containing antagomiR‐155‐5p decreased arthritis score and paw swelling as compared to PEG‐liposomes containing antagomiR‐control or systemic delivery of free antagomiR‐155‐5p. Moreover, treatment with PEG‐liposomes containing antagomiR‐155‐5p lead to the restoration of bone marrow monocytes defect 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 delivering small RNA to monocytes/macrophages, reduced joint inflammation in murine models of RA, providing a promising strategy in human disease. image
Mots clés
Rheumatoid arthritis
Collagen-induce arthritis
K/BxN Serum transfer arthritis
monocytes-derived macrophages
miR-155-5p
PEG-liposomes RA
rheumatoid arthritis CIA
collagen-induce arthritis STA
Serum transfer arthritis PEG-liposome
PEGylated-liposome M2
alternative activated macrophages BMDM
bone-marrow derived macrophages
rheumatoid arthritis
CIA
collagen-induce arthritis
STA
Serum transfer arthritis
PEG-liposome
PEGylated-liposome
M2
alternative activated macrophages
BMDM
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