Overview: A new role for an immune checkpoint
Immune checkpoint inhibitors have transformed cancer therapy by releasing the brakes on the immune system. A surprising new finding from researchers at the University of Zurich (UZH) reveals that one such brake, TIGIT, does more than help tumor-fighting immune cells—it also promotes tissue healing. This discovery could pave the way for novel treatments for fibrosis and chronic wounds, where tissue repair processes go awry.
The experiments that traced TIGIT’s healing signal
Led by Nicole Joller, a Professor of Immunology at the Department of Quantitative Biomedicine, the team explored TIGIT’s role using a mouse model of viral infection with LCMV, a common stand-in for studying immune responses. Mice lacking TIGIT suffered greater tissue damage, especially in blood vessels and the liver, compared with control animals. This suggested that TIGIT normally helps shield tissues from virus-induced injury.
Digging deeper, the researchers compared immune cells that did and did not express TIGIT. They found that only TIGIT-positive immune cells produced a specific growth factor in response to viral infection. This growth factor activated a cascade of repair mechanisms essential for tissue regeneration. Further experiments clarified how TIGIT upregulates the gene for this growth factor, linking the checkpoint directly to regenerative signaling.
How TIGIT orchestrates tissue repair
As Joller explains, TIGIT’s promotion of growth factor production in immune cells acts as a critical driver of tissue repair after viral challenge. The study identifies a hitherto unknown function of checkpoint inhibitors: by guiding innate repair programs, TIGIT helps maintain the integrity of tissues when viruses threaten damage to blood vessels, liver, and other organs. This dual role—balancing immune defense with tissue protection—adds a new layer to our understanding of how infections can cause organ injury beyond direct viral cytotoxicity.
The implications extend beyond basic science. In clinical contexts, infections such as influenza or COVID-19 are known to inflict damage on the vascular system, liver, and lungs. A clearer map of TIGIT’s healing pathway could inform strategies to mitigate such tissue injury and improve patient outcomes during severe infections.
Potential therapeutic implications
The discovery highlights promising avenues for treating tissue-damaging conditions. If TIGIT can be harnessed safely, it may be possible to accelerate tissue regeneration and repair in conditions characterized by chronic wounds or liver fibrosis, where scar tissue limits organ function. “We could potentially activate the TIGIT checkpoint to accelerate the regenerative process,” Joller notes, underscoring the potential to translate basic science into targeted therapies.
However, any therapeutic use would require careful navigation. Checkpoint inhibitors are designed to boost immune responses against cancer, and potentiating TIGIT could have complex effects on immune balance. The research team emphasizes that a nuanced approach will be essential to avoid unintended consequences such as excessive inflammation or autoimmunity while promoting tissue healing.
Balancing immune defense with tissue protection
The study contributes to a growing body of work that reconceptualizes immune checkpoints as regulators of tissue integrity, not just gatekeepers of tumor immunity. By revealing how TIGIT links immune signaling to tissue repair, the work offers a framework for developing therapies that protect against organ damage during infection while supporting regeneration in chronic wound settings.
Next steps in the tic-tac-toe of healing
Future research will aim to map the exact molecules downstream of TIGIT that drive growth factor production, determine how this pathway interacts with other healing programs, and evaluate the safety of manipulating TIGIT in animal models with disease-relevant tissue injury. If these lines of inquiry translate to humans, the ripple effects could touch conditions ranging from skin ulcers to liver fibrosis, offering precisely targeted interventions to enhance healing where it is most needed.
In Joller’s words, the work “sheds new light on the balance between immune defense and tissue protection.” It moves science a step closer to therapies that both strengthen the body’s defenses and support the healing processes that keep tissues healthy in the face of infection and chronic disease.
