Grant: Discovery Grants Program - Individual

Identification of functional links between redox homeostasis and immunityI study the biology of macrophages, which are cells contributing to immune defenses, tissue repair, elimination of dead cells and erythropoiesis. Erythropoiesis is the process by which new red blood cells (RBCs) are generated to replace senescent cells and ensure transport of oxygen to every tissue and elimination of carbon dioxide. Macrophages are essential for erythropoiesis as they nurse non-differentiated RBCs and guide their growth, survival and maturation in response to erythropoietin. In conditions of RBC loss (bleeding and others), the body increases the levels of erythropoietin to stimulate erythropoiesis, and the behavior of macrophages are changed to allow enhanced production of RBCs. The factors leading to these changes in macrophages remain unknown, and it is important to identify them and understand how they affect their biology, in order to develop strategies to stimulate the regeneration of RBCs and to cope with various conditions characterized by insufficient RBC numbers. To succeed in this research we will establish new experimental models to induce the production of RBCs in the laboratory and investigate how macrophages ensure their nursing roles in erythropoiesis. We will also investigate the impact for high levels of erythropoietin on the interactions of macrophages with forming RBCs, which are sustained by their secretion of growth factors and their expression of proteins to provide tight cell to cell contact.