Homeostasis of Langerhans and Dendritic Cells in Health and Disease

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Dendritic cells are critical components of the immune system. They detect foreign material and coordinate the immune response. Without them immunity to viruses, tumours and vaccines is severely compromised. They are important in the rejection of transplanted organs and in ‘graft versus host disease‘, a complication of bone marrow transplantation. Additionally, they multiply and accumulate in ‘histiocytosis‘, a rare but potentially fatal disease.The question we are studying is how these cells are maintained in the body. Previously they were thought to be replaced at a steady rate by cells from the blood. Recent evidence from mice suggests that they can proliferate or renew themselves but this is not known in humans. We propose to find out 1) whether human skin dendritic cells can renew themselves; 2) what controls their survival and proliferation; 3) whether they are affected by bone marrow failure. We will use normal human skin obtained from plastic surgery and small samples from patients with specific bone marrow disorders. Our experiments will help to understand how the immune system is controlled in health and disease, including bone marrow failure and transplantation. We may identify new ways to boost vaccination, prevent harmful immune responses and treat histiocytosis