Groundbreaking finding: TIGIT helps tissue repair
Researchers at the University of Zurich (UZH) have uncovered a surprising role for the immune checkpoint inhibitor TIGIT beyond its well-known function as a cancer therapy target. In a study led by Nicole Joller, the team demonstrated that TIGIT not only helps regulate immune responses during infections but also actively promotes tissue healing. This discovery could pave the way for novel treatments for fibrosis and chronic wounds, two conditions in desperate need of effective therapies.
How TIGIT supports tissue repair
Checkpoint inhibitors typically act as a braking system on immune cells, preventing excessive inflammation. In cancer therapy, blocking these inhibitors can unleash immune cells to attack tumors. The Zurich study asks a different question: what happens when these inhibitors are present and how might they influence tissue regeneration?
The researchers used mice lacking the TIGIT gene and infected them with a rodent virus (LCMV). Compared with normal mice, the TIGIT-deficient animals experienced more tissue damage, particularly in blood vessel walls and the liver. This observation confirmed that TIGIT contributes to protecting tissue integrity during viral infections and hinted at a repair-boosting role beyond merely damping inflammation.
A specific growth factor links TIGIT to healing
To understand the mechanism, the team compared immune cells bearing TIGIT with those that did not. They found that TIGIT-expressing immune cells produced a certain growth factor in response to viral infection, a molecule that activates multiple repair processes and drives tissue regeneration. Further experiments showed that TIGIT upregulates the gene encoding this growth factor, thereby promoting healing at the site of injury.
Balancing immune defense with tissue protection
“Our findings show that TIGIT promotes the production of a growth factor in immune cells—one that is critical for repairing tissue after viral infections,” Joller explains. By revealing a previously unknown function of checkpoint inhibitors, the study adds nuance to the balance between immune defense and tissue protection. This balance is particularly relevant in infections known to cause tissue damage, such as influenza and COVID-19, where damage to blood vessel walls, liver, and lungs can be consequential.
Potential therapeutic implications
The identification of TIGI T’s role in tissue repair opens exciting possibilities for treating conditions where tissue regeneration is compromised. Chronic wounds, liver fibrosis, and other fibrotic diseases involve impaired healing and excessive scarring. If TIGIT’s tissue-healing signaling can be carefully modulated, clinicians might accelerate regeneration without triggering harmful levels of immune activity.
Joller suggests a future direction in which scientists could, in certain contexts, activate the TIGIT checkpoint to hasten regenerative processes. Such an approach would aim to harness the growth factor pathway identified in the study, potentially improving outcomes for patients with persistent wounds or fibrotic tissue damage while maintaining overall immune balance.
What comes next for research and therapy
Although the findings are compelling, translating them into human therapies will require careful work. Researchers must determine how to selectively modulate TIGIT signaling to encourage tissue repair without compromising the immune system’s ability to fight infections or cancer. Additional studies will assess whether the same TIGIT-dependent growth factor pathway operates in human tissues and how it interacts with other immune checkpoints.
Bottom line
The discovery that TIGIT promotes tissue healing reframes our understanding of immune checkpoints. By tying a cancer-immunity mechanism to tissue regeneration, this research opens a promising avenue for treating fibrosis and chronic wounds. As scientists continue to map the TIGIT-centered repair pathway, patients with tissue-damaging conditions may one day benefit from therapies that both protect and heal the body’s tissues.
