Unveiling a new function for a familiar immune brake
Checkpoint inhibitors are well known for their role in cancer therapy, where they release the immune system’s brakes to attack tumor cells. In a surprising twist, researchers from the University of Zurich (UZH) have uncovered a second, equally important function: TIGIT, a checkpoint protein, promotes tissue healing. Published in Nature Immunology, the study suggests that TIGIT helps coordinate tissue repair after viral infections, with potential implications for chronic wounds and fibrotic diseases.
From immune guard to healing ally
The team began by studying mice lacking the TIGIT gene and infected them with the rodent virus LCMV. The absence of TIGIT led to greater tissue damage, especially in blood vessel walls and the liver, indicating that TIGIT normally helps protect tissues during infection. This observation laid the groundwork for exploring how TIGIT influences the repair process beyond simply preventing damage.
A specific growth factor links TIGIT to repair
Delving into the cellular details, researchers compared immune cells bearing TIGIT with those without. They found that only TIGIT-positive immune cells produced a growth factor in response to viral infection. This factor is a key driver of tissue regeneration, activating a cascade of repair mechanisms that help restore damaged tissue. Further experiments demonstrated that TIGIT upregulates the gene responsible for this growth factor, tying the signaling pathway directly to healing.
Implications for chronic wounds and fibrosis
Traditionally, chronic wounds and liver fibrosis are driven by persistent tissue damage and scarring. The discovery that TIGIT can ramp up tissue repair points to new therapeutic strategies that could accelerate healing. By modulating TIGIT signaling, it may be possible to enhance regenerative responses where they are needed most, reducing scarring and improving function in damaged organs.
Balancing defense and repair
Joller emphasizes the broader significance of these findings: “Our results illuminate the balance between immune defense and tissue protection. While immune responses are essential to fight infections, a controlled repair program is equally important to prevent lasting damage.” This balance is particularly relevant in illnesses caused by strains of influenza or coronaviruses, where tissue damage can affect blood vessels, the liver, and lungs.
Looking ahead: a new avenue for therapies
Beyond infectious diseases, the TIGIT-driven repair pathway could inspire treatments for chronic wounds, liver fibrosis, and potentially other tissue injuries. The researchers suggest that carefully activating TIGIT could accelerate regeneration without triggering excessive inflammation. As immunologists continue to map the broader network of signals that coordinate healing, TIGIT stands out as a promising target for regenerative medicine and wound care.
What comes next?
Future work will aim to translate these findings into clinical settings. Key questions include identifying the optimal way to modulate TIGIT in humans, understanding long-term safety, and determining how TIGIT interacts with other parts of the immune system during repair. If successful, this line of research could lead to innovative treatments for chronic wounds and fibrotic diseases, expanding the therapeutic use of checkpoint inhibitors beyond cancer.
