title: The transcription Factor AHR prevents the differentiation of a stage 3 innate lymphoid cell subset to natural killer cells.
abstract: Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called "stage 3" developmental intermediate minimally characterized by a CD34(-)CD117(+)CD94(-) immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that include interleukin-1 receptor (IL-1R1)-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1(hi) human ILC3s to CD56(bright)CD94(+) interferon (IFN)-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1(hi) ILC3s from differentiating into NK cells.
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Tiffany
authors: T
authors: Hughes
authors: Integrated Biomedical Graduate Program, Medical Scientist Program, The Ohio State University, Columbus, OH 43210, USA.
authors: Edward L
authors: EL
authors: Briercheck
authors: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Aharon G
authors: AG
authors: Freud
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Rossana
authors: R
authors: Trotta
authors: Integrated Biomedical Graduate Program, Medical Scientist Program, The Ohio State University, Columbus, OH 43210, USA.
authors: Susan
authors: S
authors: McClory
authors: Integrated Biomedical Graduate Program, Medical Scientist Program, The Ohio State University, Columbus, OH 43210, USA.
authors: Steven D
authors: SD
authors: Scoville
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Karen
authors: K
authors: Keller
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Youcai
authors: Y
authors: Deng
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Jordan
authors: J
authors: Cole
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Nicholas
authors: N
authors: Harrison
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Charlene
authors: C
authors: Mao
authors: Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA.
authors: Jianying
authors: J
authors: Zhang
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Don M
authors: DM
authors: Benson
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Jianhua
authors: J
authors: Yu
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Integrated Biomedical Graduate Program, Medical Scientist Program, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: michael.caligiuri@osumc.edu.
authors: Michael A
authors: MA
authors: Caligiuri
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019002:CD56 Antigen; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D053573:Receptors, Interleukin-1 Type I; D000097043:Interleukin-22; C111235:AHR protein, human; C508590:IL1R1 protein, human