Thromboxane receptor activation in dendritic cells mitigates sepsis by suppressing S100a8/a9-mediated neutrophil recruitment - PubMed
4 hours ago
- #thromboxane receptor
- #dendritic cells
- #sepsis
- Dendritic cells (DCs) play a crucial role in regulating innate and adaptive immunity during sepsis.
- Thromboxane (TX) A2 receptor (TP) expression is significantly reduced in the blood DCs of sepsis patients, correlating with increased disease severity and higher neutrophil counts.
- In murine sepsis models, DC-specific TP deficiency worsened sepsis by promoting S100a8/a9-mediated neutrophil recruitment, NET formation, and lung injury.
- Inhibition of the S100a8/a9-TLR4 axis protected TP-deficient mice from fatal sepsis.
- TP signaling suppresses S100a8/a9 expression in DCs via PKCδ-Stat1 signaling, limiting neutrophil infiltration and NET formation.
- Targeted activation of TP in DCs using the nanodrug DCpep-U-46619 effectively alleviated sepsis-induced lung injury in mice.
- The study highlights TP as a potential therapeutic target for sepsis.