Scientists Engineer Immune Cells to Reverse Autoimmune Liver Disease in Mice

Autoimmune diseases occur when the immune system mistakenly attacks healthy tissues, often involving multiple types of immune cells working together destructively. Current treatments typically target single components, yielding limited success.

Researchers at Shandong University developed an innovative approach using engineered immune cells to treat autoimmune hepatitis, a condition where the immune system attacks liver cells. They focused on T follicular helper cells, which naturally coordinate immune responses involving T cells, B cells, and dendritic cells.

The team used amino acid-derived nanoparticles to deliver genetic instructions directly to these helper cells. The nanoparticles contained self-amplifying RNA encoding two key components: Foxp3, a protein that creates regulatory immune cells, and a chimeric antigen receptor specifically targeting CYP2D6, a liver enzyme. This combination transformed the helper cells into specialized regulatory cells that could recognize and protect liver tissue while suppressing harmful immune responses.

In mouse models of autoimmune hepatitis, the engineered cells successfully migrated to the liver, recognized target liver cells, and coordinated suppression of pathogenic immune responses. The treatment restored immune tolerance and significantly reduced liver damage.

This research represents a major advancement in autoimmune disease treatment, potentially offering more comprehensive therapy than current approaches. The ability to simultaneously modulate multiple immune cell types while maintaining tissue-specific targeting could revolutionize treatment for various autoimmune conditions. However, the work remains in early mouse studies, and human applications will require extensive safety testing and clinical trials before becoming available.