Ontogeny and function of human dermal dendritic cells. (360G-Wellcome-088555_Z_09_Z)

Dendritic cells (DC) are critical agents in the induction of immune responses and potential targets of immunotherapeutic interventions. To date, human studies have largely relied on in monocyte-derived DC generated in vitro. Much less is known about migratory myeloid DC in the peripheral tissues such as the skin, lung and gut where they acquire antigen and are mobilised to the draining lymph nodes. Recent research has defined the migratory myeloid DC of the human dermis and reveals two subsets differentiated by CD1a and CD14 expression. In this proposal my goals are: 1. To investigate the relationships between primary dermal DC, inflammatory DC and monocyte-derived DC 2. To map the human DC subsets to homologous DC subsets in the mouse 3. To determine whether CD1a+ DC may be derived independently of monocytes in the steady-state 4. To determine the key functional differences between CD1a+ and CD14+ DC 5. To test whether dermal DC are in vivo loaded with melanocyte antigen s and if this can induce tolerogenic or lytic immune responses Realisation of these goals will provide new insights into the induction of immune responses and improve our understanding of ways to enhance immunotherapeutic approaches.