Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)
Mirre De Bondt1,2, Niels Hellings2, Ghislain Opdenakker3
1Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49-Box 1042, 3000 Leuven, Belgium.
Abstract:
Neutrophils are the most abundant circulating and first-responding innate myeloid cells and have so far been underestimated in the context of multiple sclerosis (MS). MS is the most frequent, immune-mediated, inflammatory disease of the central nervous system. MS is treatable but not curable and its cause(s) and pathogenesis remain elusive. The involvement of neutrophils in MS pathogenesis has been suggested by the use of preclinical animal disease models, as well as on the basis of patient sample analysis. In this review, we provide an overview of the possible mechanisms and functions by which neutrophils may contribute to the development and pathology of MS. Neutrophils display a broad variety of effector functions enabling disease pathogenesis, including (1) the release of inflammatory mediators and enzymes, such as interleukin-1β, myeloperoxidase and various proteinases, (2) destruction and phagocytosis of myelin (as debris), (3) release of neutrophil extracellular traps, (4) production of reactive oxygen species, (5) breakdown of the blood-brain barrier and (6) generation and presentation of autoantigens. An important question relates to the issue of whether neutrophils exhibit a predominantly proinflammatory function or are also implicated in the resolution of chronic inflammatory responses in MS.
Insights
Neutrophils, often underestimated in multiple sclerosis (MS), play a key role in its pathogenesis. This review explores how these innate immune cells contribute to MS development and pathology through various effector functions.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a prevalent immune-mediated inflammatory central nervous system disease.
- The exact causes and pathogenesis of MS remain incompletely understood.
- Neutrophils, abundant innate immune cells, have been historically underestimated in MS research.
Purpose of the Study:
- To review the potential mechanisms and functions of neutrophils in the development and pathology of multiple sclerosis (MS).
- To consolidate current understanding of neutrophil involvement in MS pathogenesis.
- To highlight the multifaceted roles neutrophils may play in MS.
Main Methods:
- Review of preclinical animal models of MS.
- Analysis of patient samples.
- Synthesis of existing literature on neutrophil functions in inflammatory diseases.
Main Results:
- Neutrophils exhibit diverse effector functions contributing to MS pathogenesis.
- These functions include releasing inflammatory mediators (e.g., IL-1β), degrading myelin, forming neutrophil extracellular traps (NETs), producing reactive oxygen species (ROS), breaching the blood-brain barrier, and presenting autoantigens.
- The dual role of neutrophils, potentially both pro-inflammatory and involved in resolution, is an area of ongoing investigation.
Conclusions:
- Neutrophils are significantly implicated in multiple sclerosis pathogenesis through multiple mechanisms.
- Further research is needed to fully elucidate the complex role of neutrophils in MS.
- Understanding neutrophil functions may reveal new therapeutic targets for MS treatment.
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