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

Abstract

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.