title: The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation.
abstract: Invariant natural killer T cells (iNKT cells) are innate-like T cells that rapidly produce cytokines that impact antimicrobial immune responses, asthma, and autoimmunity. These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells. The number of Th2-type effector iNKT cells is variable in different strains of mice, and their number impacts CD8 T, dendritic, and B cell function. Here we demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells through a direct induction of the CD127 component of the receptor for interleukin-7 (IL-7) and the transcription factor c-myc. LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ. Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
authors.affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Carr
authors.affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Veena
authors.initials: V
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242.
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xue
authors.affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637 bkee@bsd.uchicago.edu mvery@uchicago.edu.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kee
authors.affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637 bkee@bsd.uchicago.edu mvery@uchicago.edu.
authors.forename: Mihalis
authors.initials: M
authors.lastname: Verykokakis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D015847:Interleukin-4