Temporal dynamics of neutrophil functions in multiple sclerosis
Shishi Shen1, Shilin Wu1, Yuge Wang1
1Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Neurobiology of Disease
|November 27, 2024
Summary
Circulating neutrophils correlate with multiple sclerosis (MS) activity and severity. Targeting neutrophils, particularly their infiltration and functions like NET formation, offers a promising therapeutic strategy for MS treatment and prognosis.
Area of Science:
- Neuroimmunology
- Inflammatory diseases
Background:
- Early neuroinflammation is critical in multiple sclerosis (MS) pathogenesis.
- Neutrophils are implicated in MS lesion development, but their dynamic roles are not fully understood.
Purpose of the Study:
- To investigate the temporal functions of neutrophils in multiple sclerosis (MS).
- To evaluate neutrophils as potential therapeutic targets and prognostic markers in MS.
Main Methods:
- Correlated neutrophil counts with disease activity and severity in treatment-naïve MS patients.
- Utilized experimental autoimmune encephalomyelitis (EAE) models to study neutrophil recruitment and function.
- Assessed the impact of CXCR2 inhibition on disease progression.
Main Results:
- Positive correlation found between neutrophil counts and MS disease activity/severity.
- Neutrophil infiltration into the spinal cord occurred during the preclinical phase, disrupting the blood-spinal cord barrier (BSCB).
- During peak EAE, neutrophils mediated demyelination via NETs, cytokine release, and antigen presentation; CXCR2 inhibition reduced damage and disability.
Conclusions:
- Neutrophils play a significant, temporally regulated role in MS pathogenesis, from early BBB disruption to later demyelination.
- Modulating neutrophil infiltration and function, for example via CXCR2 inhibition, shows therapeutic potential.
- Neutrophils are promising biomarkers for MS prognosis and potential therapeutic targets.
