Thromboxane receptor activation in dendritic cells mitigates sepsis by suppressing S100a8/a9-mediated neutrophil recruitment

Dendritic cells (DCs) regulate both innate and adaptive immunity during sepsis. The thromboxane-prostanoid (TP) receptor regulates diverse biological processes, including platelet activation, angiogenesis, and immune homeostasis. TP expression was markedly reduced in the blood DCs of patients with sepsis. In murine models of sepsis induced by cecal ligation and puncture and lipopolysaccharide challenge, DC-specific TP deficiency exacerbated sepsis and lung injury. For an in-depth analysis of the molecular alterations mediated by TP in DCs, single-cell RNA sequencing (scRNA-seq) was performed using CD45+ immune cells. Bioinformatics analysis revealed that DC-specific TP deficiency promoting S100a8/a9-mediated neutrophil recruitment and neutrophil extracellular trap (NET) formation. This phenotype was confirmed by qRT-PCR, ELISA and function experiments. Thus, TP in DCs plays a role in regulating the immune balance in sepsis and may be a potential therapeutic target.