Highlights
- Increasing evidence suggest that STAT2 and STAT3 control the expression of endothelial adhesion molecules [intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1)], initiating endothelial dysfunction during sepsis and subsequently participating in vasoplegia, coagulopathy, and MOF.
- Recent studies on emergency myelopoiesis, a fundamental process accompanying the immune response during sepsis, show that STAT3 controls C/EBPβ and Fanconi C (FANCC) gene expression, which are key factors in this process.
- The involvement of the JAK–STAT pathway in myeloid-derived suppressor cell development is a key finding in sepsis-induced immunosuppression. A better understanding of JAK–STAT involvement in immune dysfunction and MOF provides novel insights into the two leading causes of death during sepsis.
Sepsis is a life-threatening condition caused by exaggerated host responses to infections taking place in two phases: (i) a systemic (hyper)inflammatory response syndrome (SIRS), participating in multiple organ failure (MOF), a major complication of septic shock, followed by (ii) a compensatory anti-inflammatory response syndrome (CARS), leading to sepsis-induced immunosuppression and resulting in late infections and long-term mortality. The Janus kinase–signal transducer and activator of transcription (JAK–STAT)-dependent signaling pathway is involved in both manifestations, hence playing a key role during sepsis. It is also involved in emergency myelopoiesis, which participates in host defense. The aim of this review is to highlight and refine the recent implications of this signaling pathway in sepsis and illustrate why its central position makes it a potential biomarker and therapeutic target.
