Targeted immune tolerance through regulatory T-cell engineering

Autoimmune and chronic inflammatory diseases remain difficult to treat because current therapies often suppress immune responses broadly rather than correcting the specific immune imbalance that drives disease. Our work focuses on this balance between protective immunity and pathological autoimmunity, particularly in the liver and intestine.

A central theme of our research is the biology of regulatory T cells, or Tregs. These cells are essential for maintaining immune tolerance, but their number, stability, survival and antigen specificity may be altered in autoimmune hepatitis, chronic inflammation and fibrosis. Understanding these mechanisms is the basis for developing more precise immunomodulatory therapies.

The aspect of gene and cell therapy that interests us most is the possibility to engineer immune regulation rather than immune destruction. In contrast to conventional CAR-T cells used in oncology, CAR-Tregs are designed to guide regulatory T cells to defined tissues or antigens, where they may locally dampen pathogenic immune responses and support tolerance. Our translational goal is to develop antigen-specific cellular strategies that control harmful immunity without unnecessarily weakening protective immune function.

This approach is relevant for autoimmune liver disease, inflammatory bowel disease, immune-related adverse events under checkpoint inhibition, and transplantation medicine. A key challenge is to make engineered Treg therapies sufficiently specific, stable, safe and clinically translatable. For this reason, our work connects mechanistic immunology, disease models, patient-related questions and cell-engineering concepts.