Langerhans cell control of early-life dermal lymphatic development shapes adult immunity

The communication between skin and draining lymph nodes is crucial for immune responses to skin insults. Lymphatic vessels play key roles in this communication by transporting antigens from skin to lymph nodes, and mechanisms that compromise dermal lymphatic function can disrupt skin immunity. Here, we show that Langerhans cells (LCs), epidermis-derived antigen-presenting cells, promote dermal lymphatic expansion and phenotype acquisition during early life. This function was mediated by PlGF (placental growth factor) and VEGF-C (vascular endothelial growth factor C), and LCs selectively shaped the transcriptional profile of lymphatic endothelial cells. Compromise of this early-life LC-mediated lymphatic expansion reduced soluble antigen flow to draining lymph nodes and T cell responses in adulthood. Our data identify a tissue-based mechanism by which LCs regulate T cells remotely across time and space and raise the possibility that immune diseases in adulthood could reflect compromise of the LC-lymphatic axis in childhood.