MAIT cells exacerbate liver fibrosis by downsizing the intrahepatic regulatory T cell compartment

However, when and how they modulate fibrogenesis in the injured liver remain unclear. Here, using the carbon tetrachloride-induced model of liver injury in MR1- and MAIT cell-sufficient and -deficient mice, we identify MAIT cells as an early driver of fibrogenesis.

The presence of MAIT cells exacerbated hepatocellular injury, myofibroblast activation, and matrix deposition early in the course of fibrosis development, but not at later stages. This was accompanied by rapid polarization of hepatic MAIT cells toward a MAIT17 phenotype and enrichment of pro-fibrotic transcriptional programs. Concurrently, MAIT cells acquired an exhaustion-associated phenotype while still retaining their effector functions.