T_H-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the T_H-17 lineage is dependent on transforming growth factor-β and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1β induced the development of human T_H-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-γ, the chemokine CCL20 and transcription factor RORγt. In situ, T_H-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human T_H-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse T_H-17 cells require distinct factors during differentiation and that human T_H-17 cells may regulate innate immunity in epithelial cells.