2. Academic Validation
  3. Regulation of macrophage efferocytosis by the CLCF1/NF-κB pathway improves neurological and cognitive impairment following CO poisoning

Regulation of macrophage efferocytosis by the CLCF1/NF-κB pathway improves neurological and cognitive impairment following CO poisoning

  • Brain Behav Immun. 2025 Mar 11:127:126-146. doi: 10.1016/j.bbi.2025.03.003.
Xudong Zhou 1,  Jingjing He 2,  Huiping Song 3,  Weiwei Zhao 4,  Rui Li 5,  Wei Han 5,  Qin Li 6
Affiliations

Affiliations

  • 1 Emergency Department, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518060, PR China; The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China.
  • 2 The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China.
  • 3 Department of Traditional Chinese Medicine II, Rehabilitation University Qingdao Central Hospital, Qingdao, Shandong 266042, PR China.
  • 4 Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, PR China.
  • 5 Emergency Department, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518060, PR China.
  • 6 Emergency Department, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518060, PR China; The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China. Electronic address: liqin701015@163.com.
PMID: 40081779 DOI: 10.1016/j.bbi.2025.03.003
Abstract

Severe carbon monoxide (CO) poisoning can induce structural and functional damage to the nervous system, resulting in persistent cognitive impairments. Properly terminating inflammation caused by neuronal damage is essential for tissue repair. Macrophages clear cell corpses and fragments through efferocytosis and produce cytokines to coordinate the immune response, thus promoting neuronal repair and regeneration. However, within the microenvironment of the CO-affected nervous system, macrophage efferocytosis is disrupted. Our study found that macrophages regulate efferocytosis by releasing Cardiotrophin-like cytokine factor 1 (CLCF1), which modulates the NF-κB pathway in both macrophages and microglia, thereby controlling inflammation and promoting nervous system repair. Furthermore, efferocytosis regulates the secretion of cytokines such as TNF-α, IL-1β, and IL-10, promoting M2 polarization of macrophages, which aids in neuronal repair and regeneration. Regulating macrophage CLCF1 expression also leads to improvements in the memory, learning, and motor abilities of rats poisoned with CO.

Keywords

CLCF1; Carbon monoxide poisoning; Efferocytosis; Macrophages; NF-κB.

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