Thesis, FRANZEN Rachelle

Abstract

Eosinophils are leukocytes that take part in innate immunity. They derive from hematopoietic precursors in the bone marrow during a process called eosinophilopoiesis. Although eosinophils are primarily known for their role in allergic and antiparasitic responses, they also contribute to diseases called eosinophil-associated diseases. In both, parasite infection and eosinophil- associated disease, the bone marrow increases its production of eosinophils in response to interleukin-5. Eosinophilia is reminiscent of emergency granulopoiesis, during which the production of neutrophils is strongly increased in the bone marrow in response to an infection. In pathologies such as hypereosinophilic syndrome (HES), a massive expansion of eosinophils is observed within the bone marrow. If the spatial organization of emergency granulopoiesis within the bone marrow has been partially described, that of eosinophils remains, to date, largely unknown. The impact of eosinophilia on the organization and dynamics of pre-existing hematopoietic niches too remainspoorly studied. In this project, we aimed to study the spatial organization of eosinophils within the intact bone marrow in the steady-state and during eosinophilia by confocal microscopy. We used reporter mice of interleukin-5 alpha receptor (IL-5Rα) expression in mice to label eosinophil linage cells and analyzed the spatial organization of the production of mature eosinophils from their hematopoietic progenitors. One fully optimized, this approach will allow the study of eosinophilopoiesis in situ both under physiological conditions and in models of eosinophil- associated diseases.