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

Autor: Caravagna C; Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France.; Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France., Jaouën A; Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France.; Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France., Desplat-Jégo S; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, Marseille, France.; Aix-Marseille Université, NICN, CNRS, UMR7259, Marseille, France.; Service d'Immunologie, Pôle de Biologie- Hôpitaux de Marseille, Marseille, France., Fenrich KK; Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France.; Faculty of Rehabilitation Medicine University of Alberta Edmonton, Alberta, T6G 2G4, Canada., Bergot E; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, Marseille, France., Luche H; Centre d'Immunophénomique CIPHE (Phenomin), Aix-Marseille Université UMS3367, INSERM, US012, CNRS UMS3367, Marseille, France., Grenot P; Centre d'Immunophénomique CIPHE (Phenomin), Aix-Marseille Université UMS3367, INSERM, US012, CNRS UMS3367, Marseille, France., Rougon G; Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France. genevieve.rougon@univ-amu.fr.; Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France. genevieve.rougon@univ-amu.fr., Malissen M; Centre d'Immunophénomique CIPHE (Phenomin), Aix-Marseille Université UMS3367, INSERM, US012, CNRS UMS3367, Marseille, France. malissen@ciml-univ-mrs.fr.; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, Marseille, France. malissen@ciml-univ-mrs.fr., Debarbieux F; Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, Marseille, France. franck.debarbieux@univ-amu.fr.; Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France. franck.debarbieux@univ-amu.fr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Mar 23; Vol. 8 (1), pp. 5146. Date of Electronic Publication: 2018 Mar 23.
DOI: 10.1038/s41598-018-22872-y
Abstrakt: 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.
Databáze: MEDLINE
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