PhD Candidate University of Western Ontario London, Ontario, Canada
Disclosure(s):
Nicole I. Wang: No financial relationships to disclose
Introduction/Rationale: Wound healing is a crucial process that occurs following tissue injury. While minor injuries typically resolve efficiently, more severe or repeated insults can lead to dysregulated repair and progression to fibrosis. In the liver, fibrosis can be initiated by a wide range of causes, including viral infection, alcohol, metabolic conditions, and autoimmune diseases. Mucosa-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes known to participate in tissue repair. However, their role in chronic liver injury and fibrosis development remains unclear.
Methods: To investigate the contribution of MAIT cells to hepatic fibrosis, we used the carbon tetrachloride (CCl4) mouse model in MAIT cell-enriched Mr1+/+ C57BL/6 (B6)-MAIT^CAST mice and MAIT cell-deficient Mr1-/- B6-MAIT^CAST mice. Mice were injected intraperitoneally with CCl4 or corn oil (vehicle) twice a week for 12 or 26 days to assess fibrosis progression over time.
Results: At day 12, CCl4-treated Mr1+/+ mice exhibited more severe liver injury, indicated by body weight loss and elevated serum alanine aminotransferase levels, compared to Mr1-/- mice. Histological analysis similarly showed increased myofibroblast activation and collagen deposition in Mr1+/+ livers at this early stage. These differences were not present at day 26, suggesting that MAIT cells predominantly influence early fibrogenesis. Flow cytometry further showed that hepatic MAIT cells upregulated PD-1 following CCl4 exposure and shifted toward a type-17 phenotype with increased IL-17A production. Moreover, CCl4-treated Mr1+/+ mice also displayed reduced hepatic regulatory T (Treg) cell accumulation compared with Mr1-/- mice, suggesting that MAIT cells suppress Treg cells during fibrosis development.
Conclusion: These findings identify a previously unrecognized MAIT cell–Treg cell axis that shapes a pro-fibrotic immune environment and highlight an early window in which MAIT cells act as key drivers of fibrogenesis
