CLCF1/NF-κB Signaling Pathway Regulates Macrophage Efferocytosis to Ameliorate Neural Damage and Cognitive Dysfunction After CO Poisoning.

Severe carbon monoxide (CO) poisoning can cause structural damage to the nervous system, leading to long-term cognitive dysfunction in patients. Correctly terminating the inflammatory response caused by neuronal damage is a prerequisite for tissue repair. Macrophages can clear the cell corpses/fragments caused by brain injury through efferocytosis, and produce cytokines to coordinate the immune response, promoting neuronal repair and regeneration. However, in the microenvironment of the nervous system affected by CO poisoning, the function of macrophages is inhibited. Our research found that CLCF1 can regulate the secretion of cytokines such as TNF-α, IL-1β, and IL-10 through the NF-κB signaling pathway, thereby affecting neural cell repair and regeneration. Simultaneously, CLCF1 can regulate the efferocytosis function of macrophages, thus controlling the degree of inflammation and assisting in the repair of the damaged nervous system. In experiments, it was observed that targeting the regulation of macrophage CLCF1 expression led to improvements in memory, learning, and motor abilities in rats poisoned with CO.严重一氧化碳（CO）中毒可造成神经系统结构损伤，导致患者出现长期认知功能障碍。抑制神经元损伤引发的炎症反应，是组织修复的必要前提。巨噬细胞可通过胞葬作用（efferocytosis）清除脑损伤产生的细胞尸体/碎片，并分泌细胞因子协调免疫应答，进而促进神经元修复与再生。然而在一氧化碳中毒累及的神经系统微环境中，巨噬细胞的功能会受到抑制。本研究发现，心肌营养素样细胞因子1（CLCF1）可通过核因子κB（NF-κB）信号通路，调控肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）及白细胞介素-10（IL-10）等细胞因子的分泌，从而影响神经细胞的修复与再生。与此同时，CLCF1还可调控巨噬细胞的胞葬作用功能，以此控制炎症程度，辅助受损神经系统的修复。实验观察显示，靶向调控巨噬细胞CLCF1的表达，可改善一氧化碳中毒大鼠的记忆、学习与运动能力。