We have recently established that three dendritic cells subsets with separate lineages co-exist in the skin. In this grant application, we propose to dissect the origin of DC populations in the skin, identify the key molecules that control their development and examine the contribution of each DC lineage to the initiation of skin anti- microbial immune responses. We believe that these results will contribute to a better understanding of the immunological cues that govern skin immune responses. These results should also contribute to the design of novel vaccine strategies.