Neutrophil extracellular traps released by CD177neutrophils aggravated inflammation and neuronal impairment post-SCI.

Abstract

Spinal cord injury (SCI) causes irreversible motor and sensory dysfunction. Initial mechanical injury breaches the blood-spinal cord barrier (BSCB), triggering a rapid influx of neutrophils. However, previous studies on neutrophils after SCI have been relatively limited, the function and heterogeneity of neutrophils need further study. Here, we identified 3 distinct neutrophil subclusters post-SCI using scRNA-seq in SCI mouse models. Additionally, elevated levels of CD177neutrophils may aggravate inflammation and neuronal impairment based on our data from SCI patients and mice models. Further in vivo and in vitro assays indicate that CD177neutrophils induce pro-inflammatory polarization of macrophages and microglia via neutrophil extracellular traps (NETs) formation in a peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS)-dependent manner thus inducing neuronal apoptosis. Additionally, bone marrow transplantation from Cd177 knockout (KO) to Cd177 wild-type (WT) mice improved functional recovery post-SCI. These findings elucidate the role of CD177neutrophils in SCI-related inflammation and highlight their potential as therapeutic targets.