Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver

Liver fibrosis is the common response to chronic liver injury, and leads to cirrhosis and its complications. Persistent inflammation is a driving force of liver fibrosis progression. Mucosal-associated invariant T (MATT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases. Here, we show that circulating MATT cells are reduced in patients with alcoholic or non-alcoholic fatty liver disease-related cirrhosis while they accumulate in liver fibrotic septa. Using two models of chronic liver injury, we demonstrate that MATT cell-enriched mice show increased liver fibrosis and accumulation of hepatic fibrogenic cells, whereas MATT cell-deficient mice are resistant. Co-culture experiments indicate that MATT cells enhance the proinflammatory properties of monocyte-derived macrophages, and promote mitogenic and proinflammatory functions of fibrogenic cells, via distinct mechanisms. Our results highlight the profibrogenic functions of MATT cells and suggest that targeting MATT cells may constitute an attractive antifibrogenic strategy during chronic liver injury.