Langerhans cells regulate immunity in adulthood by regulating dermal lymphatic development in early life

Lymphatic vessels play critical roles in this communication by transporting antigens from skin to lymph nodes, and mechanisms that compromise dermal lymphatic function can disrupt immunity. Here, we show that Langerhans cells (LCs), epidermis-derived antigen-presenting cells, have a lymphatic-regulating role in promoting dermal lymphatic expansion and phenotype acquisition during early life.

This function is mediated by PlGF and VEGF-C, and LCs have a large impact uniquely on the transcriptomic profile of lymphatic endothelial cells compared to other skin cells. Compromise of this early life LC-mediated lymphatic expansion results in reduced soluble antigen flow to draining lymph nodes and T cell responses in adulthood. Our data provide 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.