Migration and homing of DCs to lymphoid organs is pivotal for inducing adaptive immunity and tolerance. DC homing depends on the chemokine receptor CCR7. However, expression of CCR7 alone is not sufficient for effective DC migration. A second signal, mediated by prostaglandin E₂ (PGE₂), is critical for the development of a migratory DC phenotype. PGE₂ is important for inducing efficient immune responses, but, if deregulated, contributes to chronic inflammation, autoimmune diseases through Th17‐cell development and tumorigenesis. In contrast, activation of liver X receptor (LXR)α has recently been shown to interfere with CCR7 expression and migration of DCs resulting in a reduced immune response. Here, we demonstrate that PGE₂ downregulates LXRα expression in human monocyte derived as well as ex vivo DCs. Moreover, PGE₂ stimulation dampens LXR activation, auto‐regulation and LXR‐mediated gene transcription. Consequently, we show that PGE₂ enhances CCR7 expression and migration of LXR‐activated DCs. Furthermore, we provide evidence that PGE₂ signaling and LXR activation specifically elicit converse effects on CCR7 expression and DC migration. In contrast, production of MMP9, CCL4, COX‐2, and IL‐23 is solely regulated by PGE₂, but not by LXR activation, offering new perspectives for therapeutic interventions.