Targeting JAK2: Genetic and Pharmacological Inhibition Attenuates Immune-Mediated Liver Injury by Suppressing Proinflammatory Macrophage - PubMed
2 hours ago
- #immune-mediated liver injury
- #JAK2 inhibition
- #macrophage suppression
- JAK2 inhibitors fedratinib and baricitinib significantly reduced liver damage in a ConA-induced immune-mediated liver injury model by lowering serum transaminases, histopathological injury, and inflammation.
- Baricitinib's protective effects are mediated through JAK2 inhibition in macrophages, as shown by myeloid-specific JAK2 knockout mice exhibiting reduced macrophage and CD4+ T cell activation and resistance to liver injury.
- Macrophages from baricitinib-treated or JAK2-deficient mice showed less mature and activated phenotypes, with lower MHC-II and Ly6C expression, reduced inflammatory cytokine production, and higher phagocytic capacity, leading to decreased CD4+ T cell activation.
- Baricitinib demonstrates therapeutic potential in modulating immune responses and restoring hepatic homeostasis in immune-mediated liver injury, positioning it as a promising candidate for further clinical validation.