title: Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells.
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.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands. t.cupedo@erasmusmc.nl
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.forename: Natasha K
authors.initials: NK
authors.lastname: Crellin
authors.forename: Natalie
authors.initials: N
authors.lastname: Papazian
authors.forename: Elwin J
authors.initials: EJ
authors.lastname: Rombouts
authors.forename: Kees
authors.initials: K
authors.lastname: Weijer
authors.forename: Jane L
authors.initials: JL
authors.lastname: Grogan
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000196:embryology* / Q000276:immunology*; D008221:Lymphoid Tissue / Q000196:embryology / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000276:immunology; D008643:Mesentery / Q000196:embryology / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D038081:Organogenesis; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D018168:Receptors, Retinoic Acid / Q000276:immunology; D011988:Receptors, Thyroid Hormone / Q000276:immunology; D013154:Spleen / Q000196:embryology / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D019002:CD56 Antigen; D007371:Interferon-gamma; D020381:Interleukin-17; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D008233:Lymphotoxin-alpha; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000097043:Interleukin-22; C539900:RORC protein, human; C539901:Rorc protein, mouse