PI3Kg is highly expressed in cells of hematopoietic origin. It plays an important role in dendritic cell (DC) trafficking and in the activation of specific immunity. PI3Kg-/- mice showed a reduced ability to respond to chemokines, and had a selective defect in the number of skin Langerhans cells and in lymph node CD8a-DCs. In macrophages, the chemokine RANTES/CCL5 activates the small GTPase Rac1 and its downstream target PAK2. This response depends on Gi activation and largely on the subsequent triggering of PI3Kg.