Temporal dynamics of neutrophil functions in multiple sclerosis
Early neuroinflammatory injury plays a crucial role in initiating and progressing multiple sclerosis (MS). Neutrophils are forerunners to neural lesions in MS, yet the temporal alterations of their functions in MS remains unclear. This study demonstrated a positive correlation between circulatory neutrophil counts and disease activity and severity in treatment-naïve MS patients. In experimental autoimmune encephalomyelitis (EAE), we documented the recruitment of neutrophils to spinal cord during the preclinical phase, with these cells contributing to the disruption of the blood-spinal cord barrier (BSCB) during the onset of the disease. Furthermore, during the peak phase, infiltrated neutrophils promoted demyelination through formation of neutrophil extracellular traps (NETs), cytokine secretion and antigen presentation. Notably, the inhibition of neutrophil infiltration using a CXCR2 inhibitor effectively mitigated white matter damage and physical disability, underscoring their potential as therapeutic targets. In conclusion, neutrophils represent promising candidates for both disease treatment and prognosis evaluation in MS. By elucidating their temporal roles and mechanisms of action, we can potentially harness their modulation to improve patient outcomes and disease management.
Authors
- Shixiong Huang (ORCID: https://orcid.org/0000-0001-5404-4664)
- Zhanhang Wang
- Yipeng Zhao (ORCID: https://orcid.org/0009-0005-4583-6818)
- Xiaobo Sun (ORCID: https://orcid.org/0000-0001-5039-6793)
- Yanyu Chang (ORCID: https://orcid.org/0000-0002-3226-1008)
- Zhengqi Lu
- Wenxuan Sun (ORCID: https://orcid.org/0009-0005-4668-9952)
- Lizhi Xiao (ORCID: https://orcid.org/0000-0003-1419-9404)
- Shishi Shen
- Shilin Wu (ORCID: https://orcid.org/0000-0001-7060-9354)
- Wei Cai (ORCID: https://orcid.org/0000-0003-4059-4627)
- Jiaqi Zhang (ORCID: https://orcid.org/0000-0002-4656-1909)
- Chen Chen (ORCID: https://orcid.org/0000-0003-2104-534X)
- Rui Li (ORCID: https://orcid.org/0000-0001-8436-8555)
- Shaoli Zhou (ORCID: https://orcid.org/0000-0002-6604-0166)
- Wei Qiu (ORCID: https://orcid.org/0000-0001-9436-3096)
- Yaqing Shu (ORCID: https://orcid.org/0000-0003-1421-0239)
- Yuge Wang (ORCID: https://orcid.org/0000-0003-3005-6163)
Institutions
- Sun Yat-sen University (CN)
- Hainan General Hospital (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Hainan Provincial Hospital of Traditional Chinese Medicine (CN)
- Guangdong 999 Brain Hospital (CN)
Publication Details
- Journal
- Neurobiology of Disease
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1016/j.nbd.2024.106744
- Citations
- 5
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.24
Funders
- National Natural Science Foundation of China
- Sun Yat-sen University
- China Postdoctoral Science Foundation
- Guangzhou Science and Technology Program key projects
- Key Technologies Research and Development Program
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities
- Basic and Applied Basic Research Foundation of Guangdong Province