Harnessing the Power of Chlorogenic Acid: Inhibiting IL-2-Mediated Treg Upregulation to Combat Post-Traumatic...

Chlorogenic acid (CGA) exerts immunomodulatory effects by regulating the proportion of regulatory T cells (Tregs), and T-cell dysregulation is a known feature of post-traumatic osteomyelitis (PTO). This study explored the mechanism of CGA in the treatment of PTO from the perspective of T-cell immunity.

Lymphocytes isolated from rat spleens were stimulated with interleukin (IL)-2. A PTO model was established by injecting Staphylococcus aureus into the tibial marrow cavity of New Zealand white rabbits. PTO rabbits were treated with either CGA by gavage or lentiviral IL-2 injection. The Treg proportion was evaluated by flow cytometry. The expression of forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte antigen-4 (Ctla-4), and IL-2 was quantified by quantitative real-time polymerase chain reaction. The concentrations of tumor necrosis factor-α (TNF-α), IL-10, and IL-2 were measured using enzyme-linked immunosorbent assays. Micro-computed tomography and hematoxylin and eosin staining were performed to characterize bone destruction. The proliferation of CD4⁺ T/CD8⁺ T cells was evaluated by flow cytometry.

IL-2 stimulation elevated the proportion of Tregs in rat splenic lymphocytes, upregulated Foxp3, Ctla-4, and IL-10 expression, and decreased TNF-α expression (p < 0.05). PTO rabbits exhibited significant bone destruction and inflammatory cell infiltration in bone tissue. In the peripheral blood of PTO rabbits, the Treg proportion was elevated, with increased expressions of Foxp3, Ctla-4, IL-10, and IL-2, reduced TNF-α expression, and increased proliferation of CD4⁺ T/CD8⁺ T cells. These changes were significantly reversed by CGA administration (p < 0.001). However, the reversal effects of CGA were offset by exogenous IL-2 (p < 0.001).

CGA alleviates PTO by inhibiting IL-2-mediated upregulation of Tregs.