New role for checkpoint inhibitors in tissue healing
Checkpoint inhibitors are best known for unleashing the immune system against cancer. A surprising new perspective emerging from researchers at the University of Zurich (UZH) shows that one of these inhibitors, TIGIT, also plays a vital part in tissue repair. Published in Nature Immunology, the study reveals a previously unknown function of TIGIT: it promotes the production of a growth factor that drives tissue regeneration, offering potential new directions for treating chronic wounds and fibrosis.
How TIGIT supports tissue repair in viral infections
To explore TIGIT’s role beyond immune defense, scientists used a mouse model infected with the rodent virus LCMV. They compared normal mice with those lacking the TIGIT gene. The absence of TIGIT led to more tissue damage—especially in blood vessel walls and the liver—indicating that TIGIT helps shield tissues from viral injury. This finding set the stage for uncovering the molecular mechanism behind TIGIT’s protective effects.
The signaling pathway: TIGIT and growth factor production
The researchers then examined immune cells with and without TIGIT on their surfaces. They found that only immune cells containing the TIGIT checkpoint produced a particular growth factor in response to viral infection. This growth factor is pivotal for activating a broad set of repair processes and tissue regeneration. Importantly, the team demonstrated how TIGIT upregulates the gene responsible for this growth factor, linking the checkpoint inhibitor directly to tissue repair pathways.
Implications for chronic wounds and fibrosis
Beyond acute viral infections, the team’s findings have potential applications for chronic conditions characterized by tissue damage and scarring. Chronic wounds, a common and often difficult-to-treat problem, could benefit from strategies that harness TIGIT’s regenerative signaling. Likewise, liver fibrosis—where excessive scar tissue compromises organ function—might be approachable by modulating TIGIT-driven pathways to promote restoration rather than scarring.
Balancing immune defense with tissue protection
Lead researcher Nicole Joller, Professor of Immunology at the Department of Quantitative Biomedicine at UZH, emphasizes that the study sheds light on how the immune system balances defense with tissue preservation. “We could potentially activate the TIGIT checkpoint to accelerate the regenerative process,” she remarked. The work adds a new layer to our understanding of how immune regulation shapes outcomes after infections, including diseases such as influenza or COVID-19 that can cause vascular and organ damage.
What comes next for research and therapy
The discovery opens avenues for developing therapies that selectively harness TIGIT-driven tissue repair while preserving necessary immune defense against pathogens and tumors. Future research will need to determine how to safely target this pathway in humans, identify potential side effects, and explore how TIGIT interacts with other checkpoints in the context of chronic inflammatory diseases. If successful, these strategies could complement existing treatments for chronic wounds and fibrotic diseases, offering renewed hope for patients who currently have limited options.
Conclusion
The study from UZH marks a milestone in immunology by proving that natural immune brakes like TIGIT not only protect against excessive inflammation but also actively promote tissue healing. As scientists continue to map the exact mechanisms and downstream effects, TIGIT could become a central node in therapies designed to repair damaged tissues and restore function in chronic conditions.
