Human fetal lymphoid tissue–inducer cells are interleukin 17–producing precursors to RORC+ CD127+ natural killer–like cells

Mouse lymphoid tissue–inducer (LTi) cells require the transcription factor RORγt. Cupedo's group identifies RORγt + human LTi cell equivalents as committed natural killer cell precursors, and teams led by Vivier and Diefenbach describe RORγt-expressing interleukin 22–producing natural killer cells in mouse gut. The human body contains over 500 individual lymph nodes, yet the biology of their formation is poorly understood. Here we identify human lymphoid tissue–inducer cells (LTi cells) as lineage-negative RORC + CD127 + cells with the functional ability to interact with mesenchymal cells through lymphotoxin and tumor necrosis factor. Human LTi cells were committed natural killer (NK) cell precursors that produced interleukin 17 (IL-17) and IL-22. In vitro , LTi cells gave rise to RORC + CD127 + NK cells that retained the ability to produce IL-17 and IL-22. Postnatally, similar populations of LTi cell–like cells and RORC + CD127 + NK cells were present in tonsils, and both secreted IL-17 and IL-22 but no interferon-γ. Our data indicate that lymph node organogenesis is controlled by an NK cell precursor population with adaptive immune features and demonstrate a previously unappreciated link between the innate and adaptive immune systems.