Leucocyte and Pathogen Trafficking through Lymphatics in Inflammation and Immunity

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We are investigating how cells enter and move within lymphatic vessels so that in the future we can develop new therapies to block inflammation, prevent tumour spread, and make the delivery of vaccines to emerging infections more efficient. The lymphatic vessels form a dense network that intertwines the blood circulation and whose main functions are to maintain fluid balance and to transport cells carrying foreign antigen to the lymph nodes where they meet T and B cells and stimulate the immune response. Importantly, the lymphatics also contribute to diseases such as cancer by allowing metastatic tumours (e.g. skin and breast cancer) to spread to other parts of the body, and they act as a reservoir for malignant cells. Even though the involvement of lymphatics in disease have been known for a long time, their biology is still not well understood and so research in my group is dedicated to understanding how immune cells and tumours enter and navigate within the lymphatics. Thus far we have discovered that in inflammation, entry of immune cells carrying proteins from infectious agents depends critically on recognition of inflammation-induced protein receptors on the surface of lymphatic vessels, and that this is obligatory for the generation of the immune response to infection. We have also identified a separate mechanism that controls tumour cell entry to the lymphatics during lymph node metastasis in murine tumours and humans. We are also particularly interested in researching a molecule in lymphatics called LYVE-1 and we anticipate that further research in this area will reveal new ways to block inflammation, and to promote protective immunity to emerging infectious agents by enhancing vaccine delivery.