Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. Sepsis is characterized by an inappropriate inflammatory response while neutrophils exert an important role in the excessive inflammatory response. The discovery of specialized pro-resolving mediators (SPMs) provides a new direction for the treatment of a series of inflammatory-related diseases including sepsis. Among them, the regulation of Maresin1 on immune cells was widely demonstrated. However, current research on the regulatory effects of Maresin1 on immune cells has remained at the level of certain cell types. Under inflammatory conditions, the immune environment is complex and immune cells exhibit obvious heterogeneity. Neutrophils play a key role in the occurrence and development of septic lung injury. Whether there is a subpopulation bias in the regulation of neutrophils by Maresin1 has not been elucidated. Therefore, with the well-established cecal ligation and puncture (CLP) model and single-cell sequencing technology, our study reveals for the first time the regulatory mechanism of Maresin1 on neutrophils at the single-cell level. Our study suggested that Maresin1 can significantly reduce neutrophil infiltration in septic lung injury and that this regulatory effect is more concentrated in the Neutrophil-Cxcl3 subpopulation. Maresin1 can significantly reduce the infiltration of the Neutrophil-Cxcl3 subpopulation and inhibit the expression of related inflammatory genes and key transcription factors in the Neutrophil-Cxcl3 subpopulation. Our study provided new possibilities for specific modulation of neutrophil function in septic lung injury.
Keywords: Maresin1; cellular heterogeneity; neutrophils; sepsis-induced lung injury.