Fubao Liu

The purpose of this study was to explore the associated mechanism by which MSCs-derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)-derived exosomes were administrated into LO2 cells exposed to hypoxia/reoxygenation (H/R) and mice subjected to IRI. Cell viability was assessed by CCK-8 assay. Apoptosis was analyzed by flow cytometry and TUNEL staining. The expression of miR-1246 and Wnt/β-catenin pathway-related proteins was detected by quantitative real-time PCR (qRT-PCR) and western blotting. The concentration of pro-inflammatory cytokines was determined by ELISA. Luciferase activity assay was performed to confirm the interaction between miR-1246 and glycogen synthase kinase 3β (GSK3β). Hepatic function was assessed by determining serum alanine amino transferase (ALT) and aspartate amino transferase (AST) levels. Histological changes were observed using hematoxylin-eosin (H&E) staining. MiR-1246 was significantly downregulated in H/R-treated LO2 cells. Treatment with exosomes derived from hUCB-MSCs led to miR-1246 upregulation. Furthermore, hUCB-MSCs-derived exosomes induced anti-apoptotic and pro-survival effects in LO2 cells and ameliorated IRI-induced hepatic dysfunction in mice, while treatment of exosomes from miR-1246 inhibitor-transfected hUCB-MSCs showed opposite effect, which was mediated by regulating GSK3β-Wnt/β-catenin pathway. Collectively, hUCB-MSCs-derived exosomes alleviated hepatic IRI by transporting miR-1246 via regulating GSK3β-mediated Wnt/β-catenin pathway.

The purpose of this study was to explore the mechanism by which human umbilical cord blood mesenchymal stem cells (hUCB‐MSCs)‐derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). hUCB‐MSCs‐derived exosomes were administrated into hepatic IRI mice or cocultured with naïve CD4⁺ T cells exposed to hepatic hypoxia/reoxygenation microenvironment. Hepatic function was assessed by determining serum transaminases. Histological changes were observed using hematoxylin and eosin staining. The proportion of T helper 17 (Th17) and regulatory T (Treg) cells were analyzed by flow cytometry. The concentration of inflammatory cytokines was determined by enzyme‐linked immunosorbent assay. The interaction between miR‐1246 and interleukin 6 (IL‐6) signal transducer (also known as gp130) was verified by luciferase activity assay. The miR‐1246 expression, Th17/Treg‐related genes, and gp130‐signal transducer and activator of transcription 3 (STAT3) pathway were detected by quantitative real‐time polymerase chain reaction and western blotting. hUCB‐MSCs‐derived exosomes ameliorated IRI‐induced hepatic dysfunction and decreased Th17/Treg ratio in CD4⁺ T cells in vitro, whereas treatment of hUCB‐MSCs with miR‐1246 inhibitor showed opposite effects, which was mediated via the IL‐6‐gp130‐STAT3 pathway. hUCB‐MSCs‐derived exosomes could alleviate hepatic IRI through modulating the balance between Tregs and Th17 cells via miR‐1246‐mediated IL‐6‐gp130‐STAT3 axis.

Liver‐resident natural killer (LrNK) cells are a unique subset of NK cells that are distinct from conventional NK cells. However, little is known about the mechanisms by which LrNK cells mature. In this study, we discovered that LrNK cells exhibit a relatively immature phenotype and impaired cytotoxic capacity in the absence of CD8⁺ T cells. The provision of CD8⁺ T cells to Cd8‐/‐ or Rag1‐/‐ mice led to the restoration of LrNK cell maturation. Furthermore, co‐culture with CD8⁺ T cells induced immature CD27⁺ LrNK cells to convert into mature CD27^‐ LrNK cells, whereas blocking the interaction of CD70 and CD27 abrogated the ability of CD8⁺ T cells to promote the maturation of LrNK cells. Conclusion: Our findings indicate that CD8⁺ T cells promote the maturation of LrNK cells through the CD70‐CD27 axis, and therefore highlight a previously unknown mechanism responsible for the mediation of LrNK cell maturation.