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Transcriptional regulation of phagocytosis in macrophages

Objective

Macrophages are one of the most enigmatic cell types of our body. The regulation of the macrophage phagocytic activity is of utmost importance for a variety of processes, ranging from the formation and maintenance of tissues to the clearance of cellular debris. Yet little is known of the regulation of this process. Like those isolated from tissues, macrophages differentiated from monocytes ex vivo contain cells that don't show phagocytosis. We aim to develop methods to separate the fractions based on their ability to phagocytose. If monocytes are treated with dexamethasone in the early phase of the ex vivo maturation process, the fraction of macrophages showing phagocytic activity increases from 25-40% to 60-75%. Dexamethasone is known to act through a member of the nuclear hormone receptor family. This strengthens our hypothesis that the ability to phagocytose needs transcriptional reprogramming at some stage of the macrophage development.

We will compare the transcriptomes of the phagocytosing and non-phagocytosing cells, as well as those that were matured in the presence or absence of this glucocorticosteroid analogue. Both approaches are expected to yield a limited subset of differentially expressed genes with a substantial overlap. This will enable us to identify molecular markers to distinguish the two populations, and may define the machinery that underlies the differential phagocytic ability. We aim to investigate the in vivo effect of dexamethasone on the macrophage phagocytic capacity in mice. To this end, we will treat mice with dexamethasone and assess the phagocytic capacity of peritoneal macrophages at appropriate time points upon challenge with thioglycolate, a substance known to induce infiltration of macrophages to the peritoneal space. This mouse system will allow us to validate the roles of candidate genes from our transcriptome study, provided appropriate KO models will be available.

Call for proposal

FP6-2004-MOBILITY-12
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Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

UNIVERSITY OF DEBRECEN
Address
Egyetem Tér 1.
Debrecen
Hungary