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

Figure 1 Mechanisms underlying the hepatoprotective effects of rapamycin nanoparticles in primary biliary cholangitis[13]. A: Intraperitoneal injection of nanoparticles encapsulating rapamycin (ImmTOR) in primary biliary cholangitis (PBC) mice resulted in inhibition of mechanistic target of rapamycin signaling, suppression of autoreactive B and T lymphocytes, reduction of anti-mitochondrial antibodies, and decreased levels of pro-inflammatory cytokines. These effects ultimately led to improvements in liver pathology and function. Notably, ImmTOR may also induce upregulation of autophagy in hepatic cells and bile duct cells (BDCs), thereby enhancing autophagy-mediated clearance of apoptotic BDCs and contributing to reduced inflammation and anti-mitochondrial antibodies production. Additionally, ImmTOR may promote the expansion of regulatory T cells, which exert anti-inflammatory effects; B: Inflammatory cell infiltration around damaged BDCs in the liver of untreated PBC mice (indicated by arrows); C: Liver of an ImmTOR-treated PBC mouse with reduced inflammation, the green dotted arrows indicate mechanisms proposed for future research. B and C: Citation: Yang YS, Li XR, Wang ZM, Zheng L, Li JL, Cui XL, Song YB, Ma JJ, Guo HF, Gao LX, Zhou XH. Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis. World J Hepatol 2025; 17: 104073. Copyright© The Authors 2025. Published by Baishideng Publishing Group Inc. This article is an open-access article. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/. IP: Intraperitoneal; ImmTOR: Nanoparticles encapsulating rapamycin; PBC: Primary biliary cholangitis; mTOR: Mechanistic target of rapamycin; Treg: Regulatory T; AMA: Anti-mitochondrial antibodies; BDC: Bile duct cell.