On April 4, 2026, a research team led by Professor Songmin Ying and Associate Professor Qian Wu from the Center for Reproductive Medicine at Zhejiang University International Institute of Medicine (ZJU-IIM), together with Professor Fudi Wang from the School of Basic Medical Sciences, Zhejiang University, published a cover-featured study in the prestigious journal Science Immunology. Titled “Copper supports regulatory T cell energetic state to sustain peripheral immune tolerance”, the study reveals a novel mechanism for controlling regulatory T cell function.
Regulatory T cells (Treg cells), known as the "brakes" of the immune system, play a central role in maintaining immune tolerance and stabilizing tissue homeostasis. Dysfunction of these cells is closely associated with a variety of diseases, including autoimmune diseases and cancer. At present, the clinical application of Treg adoptive transfer is limited by insufficient functional stability in vivo, resulting in suboptimal clinical efficacy.
In this study, the research team found that Treg cells in a high-energy state exhibited stronger immunosuppressive activity. Further investigations revealed that copper metabolism constitutes the core upstream pathway governing the energy status of Treg cells. Among these, the copper transporter Slc31a1, a critical copper importer in Treg cells, plays an indispensable role in maintaining their normal function.
To verify this conclusion, the researchers generated mice with Treg-specific deletion of Slc31a1.
Results showed that Slc31a1-deficient Treg cells exhibited impaired mitochondrial function and diminished immunosuppressive activity, resulting in excessive T cell activation, systemic inflammation, and multi-organ pathological damage. Notably, the copper ionophore Elesclomol effectively alleviated these inflammatory responses and organ injuries.
This study thus highlights the therapeutic potential of targeting copper metabolism, offering a promising strategy for treating autoimmune and inflammatory diseases and overcoming the bottlenecks limiting the clinical efficacy of Treg adoptive transfer.
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