title: Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages.
abstract: Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that have important functions in protecting epithelial barriers against infections and in maintaining organ homeostasis. ILCs have been categorized into three distinct groups, transcriptional circuitry and effector functions of which strikingly resemble the various T helper cell subsets. Here, we identify a common, Id2-expressing progenitor to all interleukin 7 receptor-expressing, "helper-like" ILC lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3 lineages, but not into conventional natural killer (cNK) cells that have been considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46(+) IL-7Rα(+) ILC lineage that required T-bet for specification and was distinct of cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-γ and TNF and protected against infections with the intracellular parasite Toxoplasma gondii. Our data significantly advance our understanding of ILC differentiation and presents evidence for a new ILC lineage that protects barrier surfaces against intracellular infections.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Christoph S N
authors.initials: CSN
authors.lastname: Klose
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Flach
authors.affiliation: Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Möhle
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Max-Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Leif
authors.initials: L
authors.lastname: Rogell
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoyler
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Ebert
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Fabiunke
authors.affiliation: Genomics Lab, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Fonseca-Pereira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Rita G
authors.initials: RG
authors.lastname: Domingues
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga-Fernandes
authors.affiliation: Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany; BIOSS, Centre of Biological Signalling Studies, Albert Ludwigs University Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Arnold
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohrgasse 7, 1020 Vienna, Austria.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.affiliation: Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Ildiko R
authors.initials: IR
authors.lastname: Dunay
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Yakup
authors.initials: Y
authors.lastname: Tanriver
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany. Electronic address: diefenbach@uni-mainz.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007113:Immunity, Innate; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D020395:Receptors, Interleukin-7