Immune consequences of red cell ageing, death and disposal (360G-Wellcome-094847_Z_10_Z)

There is increasing recognition of the clinical importance of red blood cell (RBC) ageing and clearance, including in transfusion medicine, but the consequences of disposal remain poorly understood. Several mechanisms of recognition and immune clearance of aged RBC have been described, but their effects, particularly on the immune system, and relevance to disease need urgently to be determined. This will be the first comprehensive programme to characterise the immune consequences of effete RBC clearance in health and disease. The specific goals are to define the consequences of RBC uptake on phagocyte and immune responses; establish how storage of blood collected for transfusion modifies these responses; determine the age-related changes to RBC that mediate immune effects; identify the sites and cells mediating clearance in vivo; and ascertain the effects of abnormal clearance in exemplar inherited and acquired diseases. This timely application assembles sophisticated techniques av ailable locally and through key external collaborations, and builds on an ongoing partnership between the University of Aberdeen and the Scottish National Blood Transfusion Service. The results will be of direct clinical relevance to many diseases affecting RBC lifespan, and the conclusions will inform knowledge of cell turnover more generally.