title: Human RORγt(+)CD34(+) cells are lineage-specified progenitors of group 3 RORγt(+) innate lymphoid cells.
abstract: Group 3 innate lymphoid cells (ILC3s) are defined by the expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34(+) hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt(+)CD34(+) HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt(-)CD34(+) HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt(+)CD34(+) cells are lineage-specified progenitors of IL-22(+) ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.
authors.affiliation: Department of Experimental Medicine, University of Genova, Via LB Alberti 2, 16132 Genova, Italy; UOC Immunologia, IRCCS-AOU-San Martino-IST, L.go R. Benzi 10, 16132 Genova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Montaldo
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Luiz Gustavo
authors.initials: LG
authors.lastname: Teixeira-Alves
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Timor
authors.initials: T
authors.lastname: Glatzer
authors.affiliation: Cell Biology, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Durek
authors.affiliation: Cell Biology, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Stervbo
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hamann
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B. Branchetta 20a, 51000 Rijeka, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Babic
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Paclik
authors.affiliation: HNO-Klinik-Charité-Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stölzel
authors.affiliation: Klinik für Allgemein-, Gefäß- und Thoraxchirurgie Charité-Universitätsmedizin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Gröne
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Lozza
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany; Immune System, Berlin-Brandenburg Center for Regenerative Therapies (BCRT) Charité-Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Juelke
authors.affiliation: Immune Regeneration and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT) Charité-Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Matzmohr
authors.affiliation: Giannina Gaslini Institute, Via G. Gaslini 5, 16147 Genova, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loiacono
authors.affiliation: Giannina Gaslini Institute, Via G. Gaslini 5, 16147 Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Petronelli
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, 1G Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Nicholas David
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: Giannina Gaslini Institute, Via G. Gaslini 5, 16147 Genova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Department of Experimental Medicine, University of Genova, Via LB Alberti 2, 16132 Genova, Italy; UOC Immunologia, IRCCS-AOU-San Martino-IST, L.go R. Benzi 10, 16132 Genova, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ) Berlin, Leibniz-Gemeinschaft, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: romagnani@drfz.de.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D007694:Killer Cells, Natural / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D046228:Microarray Analysis; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D014066:Palatine Tonsil / Q000276:immunology; D015398:Signal Transduction; D000097043:Interleukin-22
chemical_list: D018952:Antigens, CD34; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000097043:Interleukin-22