Characterization of the myeloid cells in different brain interfaces during neuroinflammation
Abstract: Macrophages in CNS interfaces (cpM, mM and pvM, collectively called CAMs) where long time believed to be myeloid cells that maintain their population with a turnover from blood monocytes. This view changed recently, as it was discovered that under homeostasis these macrophages are in fact long living myeloid cells with a yolk sac origin and have almost no long term contribution from blood monocytes. Kinetics and morphology of CAMs in neuroinflammatory diseases are still unclear when yolk sac origin is one of the parameters considered in the evaluation We established a method to describe eight populations of CNS myeloid cells via surface antigens and evaluated the accuracy of this FACS based approach. While under homeostasis the differentiation of cell populations was very accurate, we saw a high influx of Ly6C+ monocyte-derived cells to our CD64+MerTK+ macrophage population when we tested the model under the pathological conditions of experimental autoimmune encephalitis (EAE). Since EAE lesions in the CNS show a high density of myeloid cells we further evaluated the contribution of monocyte-derived inflammatory macrophages and resident CAMs to this increase. We used a Cx3cr1Cre-ERT2 : R26Tomato based mouse model, that allowed us to separately evaluate CAMs and inflammatory macrophages under EAE conditions. When we found monocyte-derived inflammatory macrophages to be the main cause for a high myeloid cell density in CNS lesions, we tried to evaluate their capacity to proliferate under EAE and found a significant increase in their proliferation capacity. Finally we tried to get further information on the correlation between cell-morphology and EAE disease stage in different CNS interfaces and found a non-significant change in morphology that maybe can be linked to disease stage. Altogether myeloid cells of the CNS are very diverse and their surface markers show changes when different conditions are applied in experimental setups. We concluded that experiments targeting myeloid populations while considering their YS origin should be done with core signature gene profiling instead of long established surface marker experiments, to get more accurate insight on functions and kinetics
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Universität Freiburg, Dissertation, 2020
- Keyword
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Cells
Brain
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2020
- Creator
- DOI
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10.6094/UNIFR/155486
- URN
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urn:nbn:de:bsz:25-freidok-1554861
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:41 PM CET
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
Time of origin
- 2020