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New research identifies pathway to reversing liver fibrosis
By Houda Houbeish
Study shows how specialized immune cells contribute to liver scarring, pointing to new possibilities for early treatment
By Houda Houbeish
A new study by Western University researchers has identified a potential pathway to reversing liver fibrosis, a condition that can progress to life-threatening liver disease.
Published in Sciences Advances, the findings demonstrate how specialized immune cells, known as mucosa-associated invariant T cells (MAIT cells), contribute to liver scarring – and how targeting them could help mitigate or reverse the damage.
“Traditionally, MAIT cells have been studied primarily for their ability to fight infections, but much less was known about their roles in tissue injury, repair and scarring,” said Nicole Ilayda Wang, a PhD candidate in microbiology and immunology at Western’s Schulich School of Medicine & Dentistry. “Our findings reveal a previously underappreciated role for these cells in chronic liver disease and fibrosis development.”
Liver fibrosis develops when ongoing damage leads to a buildup of scar tissue. In the liver, too much scar tissue can disrupt blood flow and impair liver function.
“Tissue fibrosis, including liver fibrosis, can result from exposure to chemicals or toxins, viral infections such as COVID, metabolic stress, and autoimmune and inflammatory diseases. It affects millions of people worldwide,” said Mansour Haeryfar, PhD, professor of immunology.
Liver fibrosis can progress to cirrhosis, or severe liver scarring, a life-threatening condition. According to the Government of Canada, liver disease and cirrhosis ranked among the 10 leading causes of death in Canada in 2024.
“There is an unmet need for early interventions to reverse fibrogenic processes before it is too late,” said Haeryfar.
Using preclinical mouse models and data from patients with fibrosis, Wang and Haeryfar investigated the role of MAIT cells in liver scarring.
They discovered an interaction between MAIT cells and regulatory T cells, immune cells that normally help keep inflammation under control.
Their findings showed that MAIT cells worsen fibrosis by inhibiting regulatory T cells.
“MAIT cells are best known for their antimicrobial properties. However, we found them to be pathogenic in this context,” said Haeryfar. “Mechanistically, they reduce regulatory T lymphocyte numbers in the liver, worsening fibrosis.”
In addition to being the first to explain the exact role that MAIT cells play in fibrogenic processes, the study also shows that targeting MAIT cells therapeutically by inhibiting their activity can reduce liver fibrosis when intervention occurs in the earliest stages of the disease.
“Our findings suggest that timing is critical, as targeting these cells early in the course of disease development may be particularly important for achieving therapeutic benefits,” said Wang.
A better understanding of MAIT cells could also help researchers develop treatments for other diseases, including cancer, where these immune cells play different roles.
“There is growing interest in treatments that use the immune system to fight disease. In cancer, for example, the goal is to help immune cells attack tumours,” said Wang.