IRR PhD researcher Jennifer Cartwright and colleagues, have shown that immune cells called ‘neutrophils’, contribute both to liver injury and later, resolution and repair. These findings may accelerate the discovery of neutrophil-targeted therapies for patients with inflammatory conditions. Acetaminophen (commonly known as paracetamol) overuse is the leading cause of acute liver failure (ALF) in the Western world. While early treatment can be effective, people who seek treatment late, often face poor outcomes. One key player in this liver failure is the body’s immune cell, the neutrophil - one of the body's first line of defence against infection, with many different functions. Our findings address the longstanding and continued controversy surrounding the role played by neutrophils in acetaminophen-induced acute liver injury, and highlight the importance of considering neutrophil’s dual action and timing, for therapeutic targeting. Jennifer Cartwright IRR PhD researcher and paper’s first author In patients that have ALF caused by acetaminophen medication, high numbers of neutrophils are found in the blood and liver early on, where they contribute to inflammation and liver damage. Surprisingly, neutrophils in these patients also show reduced function, which increases the risk of life-threatening bacterial infections. It has not previously been known whether neutrophils play a damaging or reparative role in these patients.Neutrophils are both damaging and reparative in ‘acetaminophen-induced acute liver injury’To investigate the role of neutrophils over the course of acetaminophen-induced acute liver injury, researchers used a drug to remove neutrophils in mice at different time points (during both the damage phase and repair phase) to study the effect. They found that neutrophils have a dual role. When neutrophils were removed early, liver damage was reduced; when they were removed later, the liver’s ability to repair itself was impaired. This suggests that neutrophils are harmful at first but helpful later, playing a key role in both causing and healing the liver damage.Neutrophils repair the liver in many waysJennifer Cartwright and colleagues also produced genetically modified mice deficient in neutrophil activation, which allowed them to identify pathways crucial for liver repair. They discovered disruptions in the production of proteins for the extracellular matrix, a biological scaffold that surrounds and supports the cells in tissue, and a decrease in the expression of genes related to blood vessel formation. They also found that neutrophils must communication effectively with other immune cells, such as monocytes and macrophages, to promote anti-inflammatory behaviour. Jennifer Cartwright (PhD researcher and paper’s first author) (right) with Adriano Rossi (supervisor) (left) at the American Association of Immunologists in Hawaii, 2-7 May 2025, where they presented the finalised work for the first time. This work was support by the Wellcome Trust and Medical Research Council (MRC) UK.Read the full paper in JHEP ReportsJennifer Cartwright profileAdriano Rossi profile Tags CIR Publication date 30 Jun, 2025
