How fat in our liver triggers inflammation

Sonja Marinović, Maya Lenartić and Karlo Mladenić have unravelled some of the earliest immunological processes leading to liver inflammation in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is a condition that impacts more than a quarter of the global population. In most people this disease only causes benign fat accumulation in the liver, but a large fraction of patients inflammation is induced. When this inflammation becomes chronic, it can cause liver fibrosis and even progress to cirrhosis and death. To date, little was known about what triggers inflammation in some patients and not others. Sonja, Maya and Karlo show that metabolically stressed liver cells upregulate a protein that activates the receptor NKG2D on immune cells. This signal initiates an inflammatory cascade that ultimately results in severe liver damage. Blocking this signal prevented development of fibrosis.

Read this story in full here: NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis | Science Immunology

NKG2D mediates fibrosis in patients with steatotic liver disease