Rapamycin nanoparticles suppress autoreactive lymphocytes and reduce anti-mitochondrial antibodies in primary biliary cholangitis: Mechanisms and implications.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts, primarily by infiltrating lymphocytes, and has limited therapeutic options. A growing body of evidence suggests that nanoparticles encapsulating rapamycin (ImmTOR) can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases. In a recent study, Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC. ImmTOR treatment reduced the expression and number of CD4+ T cells, CD8+ T cells, and B cells isolated from the liver and spleen, improved liver inflammation and enzyme levels, and was associated with a concomitant decrease in anti-mitochondrial antibody levels. In this editorial, we highlight the significance of these findings, focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels, ultimately improving liver pathology, through pathways such as mammalian target of rapamycin inhibition and autophagy restoration. We also offer a perspective on future research directions for PBC in both animal models and in vitro studies.