Background: Rheumatoid arthritis (RA)is a complex autoimmune condition influenced by multiple factors, and its underlying causes are still not fully understood. Factors such as genetics, infections, and external elements like smoking are thought to lead to immune system imbalances. Studies have shown that RA patients exhibit disruptions in immune regulation, particularly through unusual T cell behavior, with altered proliferation and differentiation of T cell subsets breaking down immune tolerance. This dysregulation is often associated with abnormal helper T cell activity, especially the overactivation of Th1 and Th17 cells [1]. Once activated, these cells produce high levels of pro-inflammatory cytokines, which aggravate synovial tissue inflammation and contribute to the acceleration of joint damage [2, 3]. These observations highlight the significant involvement of T cells in RA development and progression. T cells, particularly during their activation and differentiation, are heavily reliant on glucose as a primary energy source. When activated, T cells enhance glycolysis, a metabolic process that supplies the necessary energy for the production of inflammatory mediators [4]. Alterations in glucose metabolism within T cells have been strongly linked to RA pathogenesis, where disturbances in CD4+ T cell metabolism promote irregular proliferation and differentiation typical of RA [5]. Despite the availability of treatments like NSAIDs and DMARDs [1], many patients do not respond optimally or suffer adverse effects, emphasizing the critical need for new and more effective therapies.

Objectives: This research concentrates on evaluating the potential of mesenchymal stem cells (MSCs) as a therapeutic approach for rheumatoid arthritis (RA). Utilizing a mouse model induced with collagen to mimic arthritis (CIA), the study specifically investigates the pathways through which MSCs may influence disease progression.

Methods: A total of 28 male DBA/1 mice, aged 7 to 8 weeks, were randomly distributed into three groups: control (n=8), CIA (n=10), and MSC treatment (n=10). The CIA model was generated by intradermal administration of type II collagen along with adjuvants. On day 28 following immunization, mice in the MSC group were given 1×10^6 MSCs intravenously. Clinical assessments focused on overall health status, paw edema, and arthritis index (AI). On day 60, the mice were euthanized, and spleens were collected to determine spleen index and assess histopathological alterations via H&E staining. Immunohistochemistry was used to evaluate Ki67 expression in splenic cells. Pathological changes in both the synovium and cartilage were examined using H&E as well as Safranin O-Fast Green staining. Serum concentrations of IL-6, IL-17, TNF-α, and TGF-β were quantified through Enzyme-linked immunosorbent assay (ELISA), while lactate and pyruvate levels were measured using a colorimetric assay. Furthermore, quantitative real-time polymerase chain reaction (q RT-PCR) was performed to measure mRNA levels of FOXP3, RORγt, PU.1, GLUT1, G6PD, and PFKFB3 in splenic tissue, with analyses correlating these findings to the AI.

Results: Compared to the control group, CIA mice exhibited significant deterioration in health, including lethargy, weight loss, increased paw thickness, and elevated AI, alongside severe joint damage. In the MSC-treated group, AI was significantly reduced, splenic lymphocyte proliferation was suppressed, and RORγt and PU.1 expression levels were downregulated, while FOXP3 expression increased. Moreover, levels of pro-inflammatory cytokines (IL-6, IL-17, TNF-α) were decreased, and anti-inflammatory cytokine TGF-β was elevated, indicating an amelioration of arthritis symptoms. The MSC group also showed reduced GLUT1 mRNA expression in splenic cells. Although serum lactate and pyruvate levels showed a downward trend in the MSC group compared to the CIA group, the differences were not statistically significant ( P >0.05).

Conclusion: MSCs alleviate joint deterioration in CIA mice by reshaping T cell dynamics, including their proliferation and differentiation, while fine-tuning glycolysis. This process helps to diminish inflammation, offering valuable insights into the therapeutic mechanisms MSCs may employ in managing RA.

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[2] Chen Z, Bozec A, Ramming A, et al. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis [J]. Nature reviews Rheumatology, 2019, 15(1): 9-17.

[3] Takeuchi T, Yoshida H, Tanaka S. Role of interleukin-6 in bone destruction and bone repair in rheumatoid arthritis [J]. Autoimmunity reviews, 2021, 20(9): 102884.

[4] Chapman N M, Boothby M R, Chi H. Metabolic coordination of T cell quiescence and activation [J]. Nature reviews Immunology, 2020, 20(1): 55-70.

[5] Masoumi M, Alesaeidi S, Khorramdelazad H, et al. Role of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions [J]. Inflammation, 2023, 46(1): 88-102.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.