FIGURE 12. Model depicting the proposed role of IRF-1 in hepatic lymphocyte homeostasis and innate immune cell activation during liver transplant cold I/R injury.
IRF-1 in hepatocytes and DC is crucial in regulating both IL-15 and IL-15Rα mRNA expression and subsequent production of soluble IL-15/IL-15Rα complex by these cells. Hepatocytes are the principal producers of soluble IL-15/IL-15Rα complexes among different liver cell populations in both the steady-state and under inflammatory conditions (LTx cold I/R injury with 24 h of cold storage). Soluble IL-15/IL-15Rα complexes contribute to the homeostasis of hepatic NK, NKT, and CD8+T cells and the activation of these cells during LTx cold I/R injury determined by increased cytotoxic effector molecule expression in the liver graft (NKG2D, Granzyme B, Perforin, IFN-γ) and systemic proinflammatory markers in the recipient’s serum (IFN-γ, TNFα, IL-6). Serum ALT and AST levels significantly increase, reflecting worsened liver injury as a result of these inflammatory responses.