Summary: A new role for checkpoint inhibitors in tissue repair
Checkpoint inhibitors, best known for unleashing the immune system against cancer, may also help heal damaged tissues. Researchers at the University of Zurich (UZH) have identified a previously unknown function of one such inhibitor, TIGIT: it promotes tissue repair after viral infection. The discovery, published in Nature Immunology, could pave the way for novel treatments for chronic wounds and liver fibrosis, where tissue regeneration is often impaired.
The discovery: from protection to repair
In the body’s immune system, checkpoint inhibitors act as brakes that prevent excessive inflammation and tissue damage. Cancer therapies often remove these brakes to empower immune attack on tumors. But the UZH team investigated whether these inhibitors also participate in tissue healing. Using mice infected with the rodent virus LCMV, they found that animals lacking TIGIT suffered more tissue damage—especially in blood vessel walls and the liver—than their normal counterparts. This finding suggested that TIGIT helps limit injury and supports repair processes.
Why TIGIT matters for tissue integrity
The researchers then compared immune cells that did or did not display TIGIT. They observed that only TIGIT-positive immune cells produced a particular growth factor in response to viral infection. This growth factor is a powerful driver of tissue regeneration, activating a cascade of repair mechanisms. Further experiments revealed that TIGIT directly upregulates the gene responsible for generating this growth factor, linking the checkpoint to a specific repair pathway.
Mechanisms behind TIGIT-driven repair
Under the TIGIT-positive state, immune cells emit signals that stimulate tissue regeneration rather than solely attacking pathogens. This dual role highlights a delicate balance: while the immune system defends against infection, it also orchestrates healing to restore tissue function after injury. The study demonstrates a clear signaling pathway whereby TIGIT enhances the production of a critical growth factor, which in turn activates cells and processes essential for repairing tissue damage.
Implications for disease and therapy
The findings have broad implications beyond acute viral infections. Diseases characterized by chronic tissue damage—such as chronic wounds and liver fibrosis—could potentially benefit from therapies that modulate TIGIT activity. Joller and colleagues suggest that activating TIGIT might accelerate tissue regeneration in contexts where healing is impaired. Of course, translating these results to human patients will require careful investigation to avoid unintended consequences of immune modulation.
Potential areas of impact
- Chronic wounds: Accelerating repair in diabetic ulcers or venous ulcers by boosting TIGIT-mediated signals.
- Fibrosis: Moderating scar tissue buildup in the liver or other organs through balanced immune activation that favors regeneration.
- Infectious diseases: Reducing tissue damage from influenza, COVID-19, and other viral infections by supporting repair pathways during recovery.
Next steps and cautious optimism
While the results are promising, researchers emphasize that further work is needed to translate the TIGIT repair pathway into safe, effective therapies. The team is exploring how to selectively activate TIGIT’s tissue-protective signals without triggering adverse immune reactions. If successful, this approach could complement existing treatments for chronic wounds and fibrosis, offering new hope to patients who struggle with slow or incomplete healing.
“We could potentially activate the TIGIT checkpoint to accelerate the regenerative process,” notes Nicole Joller, Professor of Immunology at UZH. This discovery adds a new dimension to our understanding of immune checkpoints—not only as brakes on inflammation but also as engineers of tissue repair.
