Antigen-specific tolerance and control of autoimmunity effected by liver sinusoidal endothelial cells is unimpaired in liver fibrosis

作者：Gottwick C, Averhoff P, Casar C, Liebig LA, Pilz SM, Haas V, Krzikalla D, Fleischer S, Hübner N, Adlung L, Schwinge D, Schramm C, Carambia A, Herkel J · 发表于：Frontiers in immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1834595 · 研究领域：autoimmunity、immune tolerance、liver fibrosis、nanomedicine、scavenging

BACKGROUND AND AIMS: Liver sinusoidal endothelial cells (LSECs) have a key role in maintaining organismal homeostasis by scavenging blood-borne molecules and inducing specific immune tolerance to ingested antigens. The scavenger and tolerance function of LSECs can be harnessed for specific treatment of autoimmune diseases by nanoparticle-mediated autoantigen delivery to LSECs. In liver fibrosis, which is a frequent condition in human populations, LSECs undergo changes promoting pro-fibrotic and pro-inflammatory activation of other hepatic cells, but it is unclear whether the scavenger and immune tolerance functions of LSECs are affected. METHODS: Utilizing two mouse models of liver fibrosis, we explored the ability of LSECs to take up nanoparticles conjugated with antigen peptides, to present the ingested antigen peptides to T cells and to induce peptide-specific immune tolerance in vitro and in vivo in the context of autoimmune diseases. RESULTS: LSECs from fibrotic livers showed few distinct adaptations regarding immune functions; however, overall LSEC identity was largely maintained. Accordingly, endocytosis of nanoparticles by LSECs in vivo, as well as processing and presentation of nanoparticle-bound antigen peptides was not compromised by liver fibrosis. LSECs from fibrotic livers maintained the ability to effectively induce the generation of regulatory T cells from conventional CD4 T cells. Hence, targeted delivery of autoantigen peptides to LSECs in vivo effectively...