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Development and Functions of Patrolling Monocytes and Kidney Resident Macrophages

Student thesis: Doctoral ThesisDoctor of Philosophy

Mononuclear phagocytes are crucial arms of the innate immune system, performing various fonctions, from clearance of pathogenic microorganisms, to maintenance of tissue homeostasis. Two cell types have been studied; first, monocytes, bone marrow-derived cells, of which two main subsets have been described. Ly6C+ monocytes are short-lived circulating cells that have the ability to quickly migrate into tissues, and produce a range of molecules, or differentiate into inflammatory cells. Ly6Clow monocytes are a patrolling cell type, which crawls on the luminal side of vessels where they perform a monitoring of the vasculature. In a collaborative effort, using nucleoside analogs and experimentally parameterised, computer-assisted modeling, the dynamics of these two subsets has been re-examined, in the light of genetic data obtained previously in the laboratory. The results suggest that the transition between a Ly6C+ to a Ly6Clow phenotype occurs more prominently in the bone marrow, rather than the blood as suggested by the literature.
Second, macrophages in the kidney were investigated in the context of circulating small immune complexes. Macrophages are large, resident cells which develop during embryonic life, maintaining their numbers locally and independently from bone marrow-derived cells in most tissues. Kidney resident macrophages perform a constant monitoring of the circulation, in collaboration with the endothelial cells they underlie. The experimental model for the study of their response to immune complexes was studied, and the results provide insight into the unique character of this function for kidney resident macrophages, as well as clarifying the means of access of the immune complexes to the macrophages.
Together, the work presented in this thesis sheds light on particular aspects of the biology of myeloid populations, in steady state and inflammatory settings.
Original languageEnglish
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Award date2018

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