Mucosa-associated invariant T cells drive early fibrosis progression in a CCl4-induced liver injury model 2465

Description Mucosa-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes that have been shown to promote tissue repair. However, their role in the dysregulated state of fibrosis is not well understood. Therefore, we aimed to investigate the role of MAIT cells in hepatic fibrosis using the carbon tetrachloride (CCl4) mouse model of hepatic fibrosis. In this model, MAIT cell-enriched C56BL/6 (B6)-MAITCAST mice and MAIT cell-deficient Mr1-/- B6-MAITCAST mice were injected intraperitoneally with CCl4 or corn oil control twice a week for 12 or 26 days, representing time points of early fibrosis development and established fibrosis, respectively. At Day 12, CCl4-treated B6-MAITCAST mice displayed worse clinical outcomes, as evidenced by body weight loss and elevated serum alanine aminotransferase (ALT) levels compared to Mr1-/- B6-MAITCAST mice. Histological analysis revealed that CCl4-treated B6-MAITCAST mice also had increased liver myofibroblast activation and collagen deposition at Day 12. However, these differences were not present on Day 26. Flow cytometric analysis further revealed that hepatic MAIT cells were exhausted and skewed towards a Type-17 phenotype following CCl4 treatment at both time points. Together, these findings suggest that MAIT cells drive early fibrosis development through pro-inflammatory mechanisms, but their influence reduces as fibrosis progresses, indicating a time-dependent role in liver injury.