Modulation der T-Zell-Infiltration und der Aktivierung von Makrophagen/Mikroglia bei der EAE durch zellspezifische Deletion des Arylkohlenwasserstoffrezeptors (AhR)

von Mogadassa Aber
Dissertation
Datum der mündl. Prüfung:2024-08-28
Erschienen:2024-08-26
Betreuer:Prof. Dr. Christine Stadelmann-Nessler
Gutachter:Prof. Dr. Christine Stadelmann-Nessler
Gutachter:Prof. Dr. Francesca Odoardi
Gutachter:Prof. Dr. Dr. Philipp Kauffmann
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10692

 

 

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Zusammenfassung

Englisch

To better understand the pathomechanisms underlying multiple sclerosis, the role of the Ah receptor (AhR) in immune cell recruitment to the CNS was investigated using the murine experimental autoimmune encephalomyelitis (EAE) model. AhR-signaling modulates the differentiation and function of different cell populations that play an important role in neuroinflammation. AhR expression is apparent in immune cells, in particular in B-cells, T-cells, plasma cells and dendritic cells (DCs) as well as in the glial cell populations monocytes / macrophages and astrocytes. Highest expression levels can be found in the astrocytic cell population. Previous studies on EAE mice revealed that an AhR deletion leads to a reduced overall immune response. To find out which cell population is mainly responsible for this effect, cell-specific AhR knock-out mice were used (CD4+ T-cells, regulatory T-cells, DCs and astrocytes). In these mice, an active EAE was induced and the clinical course of the EAE was measured using an established scoring system of the EAE symptoms. Further histologic and immunohistochemical analysis was performed to quantify the lesion size, the T-cell infiltration and macrophage- / microglia-activation. The most pronounced effect was found in mice with an AhR-knock-out in CD4+ T-cells. Compared to control animals, those animals showed a milder clinical course, a reduced size of demyelinated lesions, decreased T-cell infiltration, as well as a reduced macrophage-/microglia-activation.
Keywords: Experimental Autoimmune Encephalomyelitis (EAE); Multiple Sclerosis (MS); Aryl-Hydrocarbon-Receptor (AhR); T-cells; astrocytes; macrophages; neuroinflammation
 
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