Related Experiment Video

Updated: Sep 29, 2025

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

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IFI16-STING-NF-κB signaling controls exogenous mitochondrion-induced endothelial activation

Shu Li1, He Xu1, Mingqing Song1

  • 1Duke Transplant Center, Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|March 24, 2022
PubMed

Insights

Mitochondria from injured cells activate endothelial cells via IFI16-STING-NF-κB signaling, promoting T cell adhesion and allograft rejection. Inhibiting this pathway offers a novel therapeutic strategy for organ transplantation.

Area of Science:

  • Immunology
  • Cell Biology
  • Transplantation Science

Background:

  • Mitochondria released from injured cells can trigger inflammation and allograft rejection.
  • The stimulator of interferon genes (STING) pathway, sensing endogenous mitochondrial DNA, activates innate immunity via NF-κB signaling.

Purpose of the Study:

  • To investigate the role of exogenous mitochondria in endothelial cell (EC) activation and immune responses.
  • To elucidate the signaling pathways involved in exogenous mitochondrion-induced EC activation and T cell adhesion.

Main Methods:

  • Exposure of endothelial cells to exogenous mitochondria in vitro.
  • Inhibition of STING, NF-κB, and IFI16 pathways.
  • Assessment of EC activation, T cell adhesion, and mitophagy.
  • In vivo studies using murine heart transplantation models.

Main Results:

  • Exogenous mitochondria activate ECs through the STING-NF-κB pathway, independent of cGAS.
  • Interferon gamma-inducible factor 16 (IFI16) mediates STING activation by exogenous mitochondria.
  • Inhibition of IFI16, STING, or NF-κB abrogates EC activation and T cell adhesion.
  • Exogenous mitochondria promote T cell-mediated rejection (CoBRR) in vivo.
  • Internalized mitochondria undergo STING-dependent mitophagy.

Conclusions:

  • IFI16-STING-NF-κB signaling regulates exogenous mitochondrion-induced EC activation and mitophagy.
  • Exogenous mitochondria contribute to allograft rejection by activating ECs and promoting T cell adhesion.
  • Targeting the IFI16-STING pathway presents a potential therapeutic strategy to reduce allograft immunogenicity.
Keywords:
NF-κBendothelial cellsinterferon gamma-inducible factor 16mitochondriastimulator of interferon genes

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