Iron and the immune response
Supervisor: Dr Hal Drakesmith
Iron is required for fundamental cellular metabolic activities including synthesis and replication of DNA, generation of energy by mitochondria, the operation of many enzymes, for carriage of oxygen, and more generally for cellular proliferation. Iron deficiency is the most common micronutrient deficiency worldwide, affecting around a billion people, especially infants and pregnant women. A familiar manifestation of iron deficiency is anaemia, whereby insufficient iron is available to support synthesis of haemoglobin, decreasing the production of red blood cells. However, recent genetic evidence demonstrates that iron is also required for the white blood cells of the immune system. Cells take up iron via the transferrin receptor (TfR1), and mutations in TfR1 that decrease iron uptake have been found to cause severe immunodeficiency and even fatality through recurrent infections. The underlying defect is believed to be due to impaired proliferation and/or functionality of responding lymphocytes, but the precise nature of the effect of iron deficiency on immunity is unknown. The mutation in TfR1 is extremely rare, but as mentioned above iron deficiency is very common, and has previously been linked with immune impairment, although available studies are old. We will investigate how iron deficiency impacts on the immunometabolism, differentiation and function of T and B cells. We will also investigate the importance of iron for dendritic cell function, because like activated lymphocytes, this cell type expresses high levels of TfR1, implying a need for iron, but unlike lymphocytes does not proliferate rapidly. Furthermore we will test whether iron supplementation can restore immunity. We will conduct these studies using in vivo and in vitro systems in Oxford and also via established collaborations with colleagues overseas in areas where iron deficiency is especially prevalent.
For further information, please contact: Prof Hal Drakesmith