Abstract
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-gamma. 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD56 Antigen / metabolism
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Cell Differentiation
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Cells, Cultured
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Humans
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Immunity, Cellular
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Immunity, Innate
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Interferon-gamma / biosynthesis
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Interleukin-17 / biosynthesis*
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Interleukin-22
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Interleukin-7 Receptor alpha Subunit / immunology
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Interleukins / biosynthesis
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Lymph Nodes / cytology
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Lymph Nodes / embryology*
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Lymph Nodes / immunology*
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Lymphoid Tissue / embryology
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Lymphoid Tissue / immunology
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Lymphotoxin-alpha / immunology
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Mesentery / embryology
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Mesentery / immunology
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Mice
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Natural Killer T-Cells / immunology*
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Organogenesis*
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Palatine Tonsil / cytology
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Palatine Tonsil / immunology
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Precursor Cells, T-Lymphoid / immunology*
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Receptors, Retinoic Acid / immunology
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Receptors, Thyroid Hormone / immunology
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Spleen / embryology
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Spleen / immunology
Substances
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CD56 Antigen
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Interleukin-17
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Interleukin-7 Receptor alpha Subunit
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Interleukins
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Lymphotoxin-alpha
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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Interferon-gamma