Abstract
Commencing with the breakdown of immune tolerance, multiple pathogenic factors, including synovial inflammation and harmful cytokines, are conjointly involved in the progression of rheumatoid arthritis. Intervening to mitigate some of these factors can bring a short-term therapeutic effect, but other unresolved factors will continue to aggravate the disease. Here we developed a ceria nanoparticle-immobilized mesenchymal stem cell nanovesicle hybrid system to address multiple factors in rheumatoid arthritis. Each component of this nanohybrid works individually and also synergistically, resulting in comprehensive treatment. Alleviation of inflammation and modulation of the tissue environment into an immunotolerant-favourable state are combined to recover the immune system by bridging innate and adaptive immunity. The therapy is shown to successfully treat and prevent rheumatoid arthritis by relieving the main symptoms and also by restoring the immune system through the induction of regulatory T cells in a mouse model of collagen-induced arthritis.
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Data availability
The data that support the findings of this study are available within the paper and the Supplementary Information. Source data are available for Figs. 1–6 and Supplementary Figs. 1, 3, 5–16, 20–23, 25–33, 35 and 36 in the associated source data file. Additional materials from this study are available from the corresponding author on reasonable request. Source data are provided with this paper.
Change history
17 November 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41565-023-01568-z
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Acknowledgements
This work was supported by the Institute for Basic Science (IBS-R006-D1) (S.K. and T.H.), a Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (21A0504L1-11) (T.H.K., S.Y.J., S.Y., J.Y. and Y.J), and a National Research Foundation of Korea (NRF) grant funded by the Korean government (2019M3A9H1103651) (H.S.S., C.K. and B.-S.K.).
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S.K., H.S.S. and T.H.K. conceived and designed the project. S.K., H.S.S., T.H.K., S. Yang, S.Y.J., S. Ye. and S.H.K. performed the experiments and analysed the data. B.C., K.S.P., H.M.S., O.K.P., C.K., M.K., M.S., J.Y., D.K. and N.L. provided technical input on this project. S.K., H.S.S., T.H.K., D.K., B.-S.K., Y.J. and T.H. wrote the manuscript. B.-S.K., Y.J. and T.H. supervised the overall research.
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Nature Nanotechnology thanks Liangfang Zhang, Mauro Perretti, and the other, anonymous, reviewer for their contribution to the peer review of this work.
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Supplementary Discussion, Figs. 1–36, unprocessed gel images for supplementary figures, gating strategy for flow cytometry, and references.
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Sequences of primers for PCR analysis.
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Koo, S., Sohn, H.S., Kim, T.H. et al. Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model. Nat. Nanotechnol. 18, 1502–1514 (2023). https://doi.org/10.1038/s41565-023-01523-y
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DOI: https://doi.org/10.1038/s41565-023-01523-y
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