title: Runx3 specifies lineage commitment of innate lymphoid cells.
abstract: Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Takashi
authors.identifier: http://orcid.org/0000-0001-7489-1051
authors.initials: T
authors.lastname: Ebihara
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Stacy H
authors.identifier: http://orcid.org/0000-0002-5448-339X
authors.initials: SH
authors.lastname: Ryu
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Plougastel-Douglas
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.|Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bern
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Egawa
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology / Q000472:pathogenicity; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050658:Core Binding Factor beta Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000209:etiology / Q000276:immunology; D007113:Immunity, Innate; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D051792:Basic Helix-Loop-Helix Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D050658:Core Binding Factor beta Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D055627:Natural Cytotoxicity Triggering Receptor 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse; C493693:Cbfb protein, mouse; C118384:Ncr1 protein, mouse; C539901:Rorc protein, mouse; C493730:Runx3 protein, mouse