Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

Abstract

Recent studies have demonstrated that the skin of a normal adult human contains 10-20 billion resident memory Tcells, including various helper, cytotoxic, and regulatory T cell subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both invitro and invivo, resting epidermal Langerhan cells (LCs) selectively and specifically induced the activation and proliferation of skin resident regulatory T (Treg) cells, a minor subset of skin resident memory Tcells. In the presence of foreign pathogen, however, the same LCs activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells' activation. These underappreciated properties of LCs, namely maintenance of tolerance in normal skin, and activation of protective skin resident memory Tcells upon infectious challenge, help clarify the role of LCs in skin.