Cytokine production by human dendritic cells - Is less more?

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Dendritic cells (DC) are specialist white blood cells responsible for initiating and coordinating immune responses against pathogens and cancer. DC act as sentinels of the immune system and are found throughout the body where they are in constant surveillance for infections or danger signals. Once armed they traffic to the lymph nodes, where they activate T lymphocytes and NK cells, which are then responsible for mounting an attack against the infection or tumour. The complex mechanisms of how dendritic cells respond to danger, and how they direct T and NK cells to induce specific immune responses appropriate for a particular infection are poorly understood. Most of our current knowledge of DC has been obtained from mouse studies, and it is believed that secretion of cytokines by dendritic cells play an important role. Human dendritic cells have been difficult to identify, however we have pioneered methods to isolate and characterise them from human tissue. We will therefore investigate the production of cytokines from human DC subsets and the role they play in the induction of immune responses. DC can be instructed in the test tube to recognise a cancer and mount an immune response, and this is a promising new therapy for cancer. Our work will uncover fundamental information about the most potent danger signal, the type of DC and the most important cytokines for inducing immune responses against cancers, and will therefore assist in the development of cancer vaccines.