Dynamics and functions of tissue-resident macrophages in the dura mater

Abstract: In the CNS and its interfaces two main population of tissue-resident macrophages exist: Microglia and CNS-associated macrophages. CNS-associated macrophages are distinguished from another by their localizations. Their distinct ontogenies, turnover dynamics and potential functions during health and disease, especially those of microglia have been investigated thoroughly in the past years. Although most studies focused on microglia, the scientific interest in CNS-associated macrophages which are located at CNS interfaces increases as CNS interfaces are more and more considered to be of immunological importance. The dura mater as well has gained scientific attention due to the rediscovery of dural lymphatic vessels. Yet, although dural macrophages represent the largest immune cell population of this important CNS interface, they are so far the least studied subpopulation of CAMs.
The aim of this study was to contribute to a better understanding about the turnover, proliferation and functions of dural macrophages during health and disease. We used transgenic Cx3cr1CreERT2/+:R26tdTomato/+ and Cxcr4CreERT2/+:R26tdTomato/tdTomato reporter mice for fate mapping studies by flow cytometry. Our results illustrated that dural macrophages were gradually exchanged by blood monocytes during homeostasis. Their turnover rate significantly increased under neuroinflammatory conditions. Furthermore using Cx3cr1CreERT2/+:R26Confetti mice we were able to explore proliferation patterns of dural macrophages during homeostasis and neuroinflammation. Analysis of the cellular distribution of dural macrophages indicated clonal expansion in homeostasis which was not upregulated upon neuroinflammation. Moreover, immunofluorescence analyses illustrated endocytosis of dextran by dural macrophages. I also demonstrated close cell contacts between infiltrated neutrophils and dural macrophages during neuroinflammation which could indicate important disease-modifying interactions between them. Furthermore, I investigated functional and morphologic aspects of dural macrophages regarding the protein Talin1 in Cx3cr1Cre/wt:Tlnfl/fl mice. In this context we found remarkably distinct cell morphologies between wildtype and Cx3cr1Cre/wt :Tln1fl/fl mice.
This thesis contributes greatly to the previous knowledge about dural macrophages especially regarding their role during neuroinflammation and provides new insight about this subpopulation of CNS-associated macrophages that so far has received little attention

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2023

Klassifikation und Themen

• Schlagwort: Makrophage

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2023
• Urheber: Fell, Amelie
• Beteiligte Personen und Organisationen: Prinz, Marco ; Amann, Lukas ; Prinz, Marco ; Henneke, Philipp ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Weitere Informationen

• DOI: 10.6094/UNIFR/240407
• URN: urn:nbn:de:bsz:25-freidok-2404073
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:48 MEZ