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Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model

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Abstract

Metabolic reprogramming of immune cells modulates their function and reduces the severity of autoimmune diseases. However, the long-term effects of the metabolically reprogrammed cells, specifically in the case of immune flare-ups, need to be examined. Herein, a re-induction rheumatoid arthritis (RA) mouse model was developed by injecting T-cells from RA mice into drug-treated mice to recapitulate the effects of T-cell-mediated inflammation and mimic immune flare-ups. Immune metabolic modulator paKG(PFK15 + bc2) microparticles (MPs) were shown to reduce clinical symptoms of RA in collagen-induced arthritis (CIA) mice. Upon re-induction, a significant delay in the reappearance of clinical symptoms in the paKG(PFK15 + bc2) microparticle treatment group was observed as compared to equal or higher doses of the clinically utilized U.S. Food and Drug Administration (FDA)-approved drug, Methotrexate (MTX). Furthermore, paKG(PFK15 + bc2) microparticle-treated mice were able to lower activated dendritic cells (DCs) and inflammatory T helper cell 1 (TH1) and increased activated, proliferating regulatory T-cells (Tregs) more effectively than MTX. The paKG(PFK15 + bc2) microparticles also led to a significant reduction in paw inflammation in mice as compared to MTX treatment. This study can pave the way for the development of flare-up mouse models and antigen-specific drug treatments.

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All data needed to evaluate the conclusions are present in the manuscript. Additional data related to this paper may be requested from the authors. The raw data required to reproduce these findings are available upon request from the authors. The processed data required to reproduce these findings are available upon request from the authors.

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Acknowledgements

The authors would also like to acknowledge the Flow Cytometry Core, the FEI at Erying Materials Center, and the Department of Animal Care and Technologies at Arizona State University.

Funding

The authors would like to acknowledge funding sources to APA that supported this work — NIH R01AR078343 and NIH R01AI155907, NIH 1R01GM144966-01 and NSF award# 2145877.

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Authors and Affiliations

  1. Department of Biological Design, Arizona State University, Tempe, AZ, 85281, USA

    Abhirami Thumsi, Joslyn L. Mangal, Abhirami P. Suresh & Abhinav P. Acharya

  2. School of Life Sciences, Arizona State University, Tempe, AZ, 85281, USA

    Srivatsan J. Swaminathan

  3. Department of Biomedical Engineering, School of Biological and Health System Engineering, Arizona State University, Tempe, AZ, 85281, USA

    Abhinav P. Acharya

  4. Department of Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA

    Abhinav P. Acharya

  5. Department of Materials Science and Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85281, USA

    Abhinav P. Acharya

  6. Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, 85281, USA

    Abhinav P. Acharya

  7. Biodesign Center for Biomaterials Innovation and Translation, Tempe, AZ, 85281, USA

    Abhinav P. Acharya

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Abhirami Thumsi designed and performed the experiments, analyzed data, and wrote the manuscript. Srivatsan J. Swaminathan and Abhirami P. Suresh performed experiments. Abhinav P. Acharya helped design experiments, procured funding, and wrote the manuscript.

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Abhinav P. Acharya is affiliated with a start-up company, Immunometabolix, LLC and VaderBio, LLC. There are no other conflicts to declare.

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Thumsi, A., Swaminathan, S.J., Mangal, J.L. et al. Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model. Drug Deliv. and Transl. Res. 13, 1925–1935 (2023). https://doi.org/10.1007/s13346-023-01333-8

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