2. Academic Validation
  3. Neutrophil extracellular traps activate STING signaling to promote dendritic cell-driven rejection after liver transplantation

Neutrophil extracellular traps activate STING signaling to promote dendritic cell-driven rejection after liver transplantation

  • Int Immunopharmacol. 2025 Jul 28:160:114763. doi: 10.1016/j.intimp.2025.114763.
Yan Wang 1,  Jie Yin 2,  Chenjiang Yu 3,  Dongdong Wu 3,  Yizhang Chen 3,  Qi Han 1,  Shipeng Li 4,  Rui Zhang 1,  Wei Wang 5,  Jun Xu 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 2 Basic Medicine School, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 3 First Clinical Medical School, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 4 Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, 450003, Henan, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: junxuty@163.com.
PMID: 40449271 DOI: 10.1016/j.intimp.2025.114763
Abstract

Purpose: Post-transplant immune rejection affects graft function. Interaction between neutrophil extracellular traps (NETs) with specific immune cells and the specific mechanism in liver transplantation were still unclear.

Method: Clinical patients RNA-Seq results were used for GSEA and KEGG analysis. C57BL/6 and C3H mouse models and clinical samples were use to describe the disease phenotype characteristics through multiple immunofluorescence, flow cytometry and etc. Cell co-culture experiments were performed to clarify the mechanism pathway process.

Results: RNA-Seq results analysis indicated that the NETs formation pathway was upregulated. Animal models confirmed that in liver transplant immune rejection status the formation of NETs in situ and peripheral cells increased and the level of cell-free DNA (cf-DNA) in peripheral cells increased. Reactive Oxygen Species (ROS) as a predisposing factor for NETs accumulated more in immune rejection status and NETs are rich in mitochondrial DNA (mtDNA). NETs promote dendritic cell maturation through STING-related pathways. NETs formation increases in patients with liver transplant immune rejection and is positively correlated with disease severity.

Conclusion: We found that NETs can regulate dendritic cell maturation through STING-related pathways after liver transplantation, which may ultimately promote the occurrence of liver transplant rejection, providing a new perspective for clinical diagnosis, treatment and prevention of liver transplant rejection.

Keywords

Dendritic cells; Immune rejection; Liver transplantation; Neutrophil extracellular traps; Reactive oxygen species; STING pathway.

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