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

First Author  Caravagna C Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  5146
PubMed ID  29572472 Mgi Jnum  J:263708
Mgi Id  MGI:6162790 Doi  10.1038/s41598-018-22872-y
Citation  Caravagna C, et al. (2018) Diversity of innate immune cell subsets across spatial and temporal scales in an EAE mouse model. Sci Rep 8(1):5146
abstractText  In both multiple sclerosis and its model experimental autoimmune encephalomyelitis (EAE), the extent of resident microglia activation and infiltration of monocyte-derived cells to the CNS is positively correlated to tissue damage. To address the phenotype characterization of different cell subsets, their spatio-temporal distributions and contributions to disease development we induced EAE in Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We combined high content flow cytometry, immunofluorescence and two-photon imaging in live mice and identified a stepwise program of inflammatory cells accumulation. First on day 10 after induction, EGFP(+) neutrophils and monocytes invade the spinal cord parenchyma through the meninges rather than by extravasion. This event occurs just before axonal losses in the white matter. Once in the parenchyma, monocytes mature into EGFP(+)/EYFP(+) monocyte-derived dendritic cells (moDCs) whose density is maximal on day 17 when the axonal degradation and clinical signs stabilize. Meanwhile, microglia is progressively activated in the grey matter and subsequently recruited to plaques to phagocyte axon debris. LysM-EGFP//CD11c-EYFP mice appear as a powerful tool to differentiate moDCs from macrophages and to study the dynamics of immune cell maturation and phenotypic evolution in EAE.
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