Unlocking a Hidden Role for Immune Checkpoints
Immune checkpoint inhibitors are best known as cancer therapies that unleash the body’s defenses against tumors. A team from the University of Zurich (UZH) has uncovered a surprising new function for one of these molecules: TIGIT, a surface receptor on immune cells, also promotes tissue healing after viral infections. This discovery could pave the way for innovative treatments for fibrosis and chronic wounds, where tissue repair processes falter.
From Guardrails to Healers: How TIGIT Works
Checkpoints act as the body’s brake system, preventing immune responses from spiraling out of control. Cancer therapies often disable these brakes to empower immune cells against tumors. But TIGIT’s role extends beyond simple restraint. In mouse models, TIGIT appears to help coordinate tissue repair by driving the production of a key growth factor that activates regeneration pathways.
UZH researchers focused on the signaling events that link TIGIT to tissue restoration. When mice faced tissue damage due to viral infection, those lacking TIGIT suffered more pronounced injury, especially in blood vessel walls and the liver. This evidenced TIGIT’s protective function in limiting tissue damage during infection.
The Signaling Pathway: TIGIT and a Growth Factor
The team compared immune cells with and without TIGIT, discovering that only TIGIT-bearing cells produced a particular growth factor in response to viral exposure. This factor is vital for tissue regeneration, turning immune cells into a source of repair signals. Further experiments revealed how TIGIT upregulates the gene responsible for this growth factor, establishing a direct link between the checkpoint and tissue healing.
Implications for Disease and Therapy
These findings illuminate the delicate balance between immune defense and tissue protection. In viral infections such as influenza or SARS-CoV-2, severe tissue damage can occur in vessels, liver, and lungs. Understanding how TIGIT promotes repair offers a new lens through which to study these injuries and their long-term consequences.
Beyond acute infections, the discovery holds promise for chronic conditions where tissue regeneration is impaired. Chronic wounds, liver fibrosis, and other fibrotic diseases could benefit from strategies that harness TIGIT’s regenerative signaling to accelerate healing and limit scar formation.
Toward Novel Therapies: Regeneration via TIGIT Activation?
Joller and colleagues view TIGIT as a potential therapeutic target not only for cancer but also for tissue repair. The idea is to modulate the TIGIT pathway to selectively enhance regeneration in damaged tissues while preserving immune balance. “We could potentially activate the TIGIT checkpoint to accelerate the regenerative process,” Joller suggests, cautiously noting that translating these findings to humans will require thorough testing to ensure safety.
As researchers continue to dissect the molecular choreography of TIGIT-driven repair, the door opens to new approaches for patients suffering from chronic wounds or organ fibrosis. The dual role of checkpoint inhibitors—as safeguards of immune balance and as promoters of healing—adds a compelling layer to the evolving field of immunology and regenerative medicine.
What’s Next for TIGIT Research?
Future studies will aim to validate TIGIT’s tissue-healing effects in additional models and to explore how this pathway interacts with other elements of the immune system. Clinical translation will depend on developing targeted strategies that leverage TIGIT’s regenerative potential without compromising immune defense against infections and cancer.
In sum, TIGIT’s newfound function in tissue repair marks a paradigm shift in how scientists view immune checkpoints. By bridging immune defense and regeneration, TIGIT could become a central player in therapies for fibrosis, chronic wounds, and beyond.
