Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) announced on Apr. 15 that active mitochondria help keep dendritic cells, which are important for the immune system, ready to respond to disease. The findings were published in Cell Metabolism and suggest new ways to improve vaccines and cancer immunotherapy.
Dendritic cells play a key role in detecting threats like infections or tumors and activating T cells, which fight these dangers. Understanding how dendritic cells stay prepared could help scientists develop better treatments for diseases where the immune response is weak or not working properly.
The study was led by David Sancho at CNIC and Stefanie K. Wculek at the Institute for Research in Biomedicine (IRB Barcelona), with Ignacio Heras Murillo as first author. The research focused on a specific mitochondrial process called electron flow through the respiratory chain, showing it is essential for keeping dendritic cells primed. This challenges previous ideas that mitochondria have only a minor role during dendritic cell activation.
Using genetically modified mouse models and human dendritic cells, researchers found that being ready does not mainly depend on energy production but rather on maintaining this electron flow. "What is remarkable is that this process is not about energy production, but about preserving the cell's internal balance, which directly shapes how genes respond to danger signals," says Ignacio Heras Murillo.
The team also discovered that disrupting electron flow changes DNA methylation patterns—molecular switches important for rapid gene activation—and identified an enzyme called TET2 as critical in this process. They showed that activating TET2 with vitamin C improved dendritic cell function in experimental models.
"These results highlight metabolism as a key regulator of immune function and suggest new strategies to boost dendritic cell activity in cancer and other diseases," adds Stefanie K. Wculek.
Restoring electron flow by introducing an alternative enzyme allowed the researchers to recover mitochondrial function without increasing energy production, helping the cells activate T cells again and control tumor growth in mice.
This research points toward targeting metabolic pathways as a way to enhance therapies based on dendritic cells, especially for cancers where immune responses are limited.
