Purinergic receptor P2Y12 boosts autoimmune hepatitis through hexokinase 2-dependent glycolysis in T cells

This study investigates the role of the purinergic receptor P2Y12 (P2RY12) in autoimmune hepatitis (AIH). The data show that P2RY12 is highly expressed in a mouse model of AIH and promotes metabolic reprogramming in T cells. The study also found that P2RY12 deficiency or inhibition reduces the expression of inflammatory mediators and protects against AIH. This suggests that P2RY12 may be a potential therapeutic target for AIH. Further analysis showed that P2RY12 prevents the degradation of hexokinase 2 (HK2) by activating the PI3K/Akt pathway and inhibiting lysosomal degradation. These findings highlight the importance of P2RY12 in regulating T cell activation and metabolism in AIH.

• 1
  P2RY12 deficiency protects mice from ConA-induced immune hepatitis by reducing serum ALT and AST levels, blocking the increases of serum IFN-γ, IL-12p70, IL-6, and TNF-α, and decreasing serum IL-10.
• 2
  P2RY12 positively regulates the activation and activity of T cells by promoting the expression of IFN-γ in CD4+ T cells and CD8+ T cells.
• 3
  P2RY12 affects HK2 stability through regulating PI3K/Akt signaling pathway and inhibiting lysosomal degradation in T cells.