Researchers at NYU Langone Health, the Chinese Academy of Sciences, and Zhejiang University have discovered an engineered protein that can turn off tissue-damaging immune cells in autoimmune diseases such as type-1 diabetes, hepatitis, and multiple sclerosis. The study, published in the journal Cell, shows that a molecule called BiTS can hold together two protein groups on T cells, including one found more often on T cells involved in autoimmune disease, thereby shutting down those T cells.
The immune system mistakenly targets the body’s own tissues instead of invading viruses or bacteria as it would during normal immune responses. Treatments focused on T cells have been elusive because blocking their action broadly weakens the immune system and creates risk for infections and cancer.
To overcome this challenge, researchers designed a molecule that attaches to two protein groups on T cells – the T cell receptor and the LAG-3 checkpoint. This attachment eliminated autoimmune tissue damage in three mouse models of disease. The study revealed an intricate mechanism that enables a careful treatment approach to T-cell driven autoimmune diseases, which currently lack effective immunotherapies.
The engineered protein works by holding TCR and LAG-3 closely together, pulling on CD3ε and disrupting its interaction with the enzyme Lck, crucial for T cell activation. This attachment allowed researchers to design a bi-specific antibody that potently suppressed T cell responses and reduced inflammatory damage in mice with type 1 diabetes and hepatitis.
The study also found that this proximity-based approach may be useful for other human diseases, including multiple sclerosis. The researchers used a mouse model of the disease and treated mice prone to developing multiple sclerosis with short-term BiTS prior to the onset of disease symptoms, resulting in reduced disease progression.
This breakthrough discovery advances our understanding of LAG-3 biology and may foster more proximity-based therapeutic designs like BiTS as immunotherapy for other human diseases.
Source: https://medicalxpress.com/news/2025-06-protein-tissue-immune-cells-autoimmune.html