title: Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage.
abstract: Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK cells (cNKs). All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNKs additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK development. Formation of the entire lymphoid and nonlymphoid type 1 ILC compartment appears to require the semiredundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes induces cNK-like properties across the lymphoid and nonlymphoid type 1 ILC compartments. Subsequent to their divergent lineage specification, hILC1s and cNKs thus possess substantial developmental plasticity.
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Olga
authors.initials: O
authors.lastname: Pikovskaya
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Julie
authors.initials: J
authors.lastname: Chaix
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Nyanza J
authors.initials: NJ
authors.lastname: Rothman
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Amélie
authors.initials: A
authors.lastname: Collins
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors.forename: Anna M
authors.identifier: http://orcid.org/0000-0001-9146-7594
authors.initials: AM
authors.lastname: Scipioni
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, INSERM U1104, CNRS UMR7280, Marseille 13288, France; and Service d'Immunologie, Assistance Publique-Hôpitaux de Marseille, Marseille 13385, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032; sr2978@cumc.columbia.edu.
authors.forename: Steven L
authors.identifier: http://orcid.org/0000-0002-1635-8619
authors.initials: SL
authors.lastname: Reiner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008822:Mice, Transgenic; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C491198:Eomes protein, mouse; C493730:Runx3 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor