title: The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor.
abstract: Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of αLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6(+) cells within the αLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Mi
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Ruhn
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D044082:Citrobacter rodentium; D004198:Disease Susceptibility / Q000276:immunology / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology; D018398:Homeodomain Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D054387:Receptors, CXCR / Q000378:metabolism; D000075744:Receptors, CXCR6; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C482906:Cxcr6 protein, mouse; D018398:Homeodomain Proteins; C497441:Nfil3 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; C493241:Rhox8 protein, mouse
keywords: bone marrow progenitor; developmental biology; immunology; innate immunity; innate lymphoid cells; intestinal immunity; mouse; stem cell; stem cells