Early involvement of peripherally derived monocytes in inflammation in an NMO‑like mouse model

Scientific Reports, 2024 · DOI: 10.1038/s41598-024-51759-4 · Published: January 23, 2024

Simple Explanation

This study investigates the role of innate immune cells, particularly monocytes, in the pathogenesis of Neuromyelitis Optica (NMO), an autoimmune inflammatory disease affecting the optic nerve and spinal cord. The research uses an NMO-like mouse model to analyze how monocytes infiltrate the brain during the early stages of the disease and contribute to inflammation through the expression of proinflammatory cytokines. By understanding the specific markers and functions of these immune cells, the study aims to identify potential therapeutic targets for NMO.

Study Duration

Not specified

Participants

Female wild-type C57BL/6N mice (12 weeks of age)

Evidence Level

Not specified

Key Findings

1
Monocytes infiltrate the brain during the early stages of NMO-like pathology and are associated with the inflammatory response.
2
Depletion of monocytes reduces the expression of proinflammatory cytokines and myelin loss in NMO lesions.
3
Infiltrated monocytes express proinflammatory genes in NMO lesions, suggesting their role in early inflammation and demyelination.

Research Summary

This study elucidates the role of blood-derived monocytes in the pathogenesis of NMO using an NMO-like mouse model. It observes marker changes in monocytes/macrophages and microglia at different time points and confirms P2ry12 as a specific marker for microglia during the acute phase. The research demonstrates that monocytes contribute to the exacerbation of NMO pathology through the secretion of inflammatory cytokines, particularly IL1b, and highlights the interplay between monocytes and microglia in influencing the disease pathology. Transcriptome analysis confirms that monocytes play a role in early inflammation and demyelination, and that microglia exhibit an inflammatory function regardless of monocyte infiltration, indicating their activation as inflammatory microglia.

Practical Implications

Targeting Monocytes

Targeting monocytes for acute management in patients with relapses could offer therapeutic potential to reduce the severity of NMO.

IL-1β Inhibition

Since monocytes induce IL-1β, targeting IL-1β may play an important role in the early stages of NMO.

Demyelination and Remyelination Regulation

In-depth research into the delayed expression of Il1b could significantly contribute to understanding the regulation of demyelination and remyelination in demyelinating diseases.

Study Limitations

1
The cellular source of delayed Il1b expression at 1 week remained unidentified.
2
Whether monocytes perform both pro-inflammatory and anti-inflammatory functions, or if distinct populations contribute to these effects, requires further detailed research.
3
Due to the disappearing pattern of the P2ry12 marker, the study was unable to determine microglia’s roles in the chronic phase.

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