The role and mechanism of FAM19A4 in promoting neutrophil activation in sepsis

Sepsis is a syndrome characterized by a dysregulated response of the host to invading pathogens which involves hemodynamic alterations that lead to multiple life-threatening organ dysfunctions and imposes a substantial global burden in terms of morbidity and mortality. Among the injured organs, the lung is the first and most frequent organ to fail. Accompanying acute respiratory distress syndrome (ARDS), which is the clinical term for acute lung injury (ALI), is one of the most critical prognostic factors for mortality in patients with sepsis. The recruitment of neutrophils to the lung makes them a key factor in the pathogenesis of ALI. Unregulated recruitment and activation of neutrophils could induce lung injury through the release of inflammatory mediators, including cytokines and reactive oxygen species (ROS). FAM19A4 is a new novel cytokine identified in 2015. In our previous study, it showed that FAM19A4 can activate neutrophils in vivo. We also indicated that the expression of FAM19A4 is upregulated in septic patients and in the murine model of sepsis. This cytokine can aggravate the lung injury and increase the mortality of mice. Thus, we supposed that FAM19A4 may recruit and activate neutrophils in lung in sepsis, and then prompt the development of sepsis-related ALI. In this study, we will identify the expression of FAM19A4 in septic patients and the model of sepsis mice. We will also clarify the influence of FAM19A4 on the sepsis-related ALI and the neutrophil function, and then explore the downstream signaling events. Our results will provide a new basis for the study of the mechanism of sepsis-related ALI and provides new targets for clinical treatment.