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

by Selleckchem | Jun 02 2023

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.

Comments：

This study describes the development of a re-induction rheumatoid arthritis (RA) mouse model to simulate immune flare-ups and assess the long-term effects of metabolically reprogrammed immune cells. The researchers tested the efficacy of immune metabolic modulator paKG (PFK15 + bc2) microparticles (MPs) in reducing clinical symptoms of RA in collagen-induced arthritis (CIA) mice.

The results showed that paKG(PFK15 + bc2) microparticles were able to delay the reappearance of clinical symptoms in the re-induction RA mouse model more effectively than Methotrexate (MTX), an FDA-approved drug commonly used to treat RA. Additionally, paKG(PFK15 + bc2) microparticles were able to reduce activated dendritic cells (DCs) and inflammatory T helper cell 1 (TH1) while increasing activated, proliferating regulatory T-cells (Tregs) more effectively than MTX. The researchers also observed a significant reduction in paw inflammation in mice treated with paKG(PFK15 + bc2) microparticles compared to those treated with MTX.

Overall, this study suggests that immune metabolic modulators such as paKG(PFK15 + bc2) microparticles may be a promising alternative or complementary treatment option for RA. Moreover, the development of the re-induction RA mouse model and antigen-specific drug treatments could further advance the understanding and treatment of autoimmune diseases. However, further studies are necessary to investigate the long-term effects and potential side effects of these treatments.