Diversity of innate immune cell subsets across spatial and temporal scales in an EAE mouse model

Céline Caravagna1,2, Alexandre Jaouën1,2, Sophie Desplat-Jégo3,4,5

  • 1Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France.

Scientific Reports
|March 25, 2018
PubMed

Insights

In experimental autoimmune encephalomyelitis (EAE), neutrophils and monocytes infiltrate the spinal cord before axonal damage occurs. These monocytes mature into dendritic cells, while microglia clear debris, offering insights into immune cell dynamics in central nervous system inflammation.

Area of Science:

  • Neuroimmunology
  • Cell Biology
  • Inflammation Research

Background:

  • Microglia activation and peripheral immune cell infiltration correlate with central nervous system (CNS) damage in multiple sclerosis and its model, experimental autoimmune encephalomyelitis (EAE).
  • Understanding the distinct roles and dynamics of these immune cell subsets is crucial for developing targeted therapies.

Purpose of the Study:

  • To characterize the phenotype, spatio-temporal distribution, and contribution of different immune cell subsets during EAE development.
  • To utilize a novel reporter mouse model for detailed in vivo analysis of immune cell dynamics.

Main Methods:

  • Induction of EAE in triple reporter mice (Thy1-CFP//LysM-EGFP//CD11c-EYFP).
  • High-content flow cytometry, immunofluorescence, and two-photon imaging in live mice.
  • Analysis of immune cell infiltration, maturation, and distribution within the CNS.

Main Results:

  • Neutrophils and monocytes invade the spinal cord parenchyma via the meninges around day 10, preceding axonal loss.
  • Monocytes differentiate into monocyte-derived dendritic cells (moDCs) in the parenchyma, peaking by day 17.
  • Resident microglia activate in grey matter and are recruited to lesions for phagocytosis of axonal debris.

Conclusions:

  • The LysM-EGFP//CD11c-EYFP reporter system effectively distinguishes monocyte-derived dendritic cells from macrophages in EAE.
  • A stepwise accumulation and maturation program of inflammatory cells occurs during EAE.
  • This study provides a dynamic view of immune cell evolution and contribution to tissue damage in EAE.

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